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1. Genetic Specificity of Hippocampal Subfield Volumes, Relative to Hippocampal Formation, Identified in 2148 Young Adult Twins and Siblings

Author: Hansell, Narelle K, Strike, Lachlan T, van Eijk, Liza, O'Callaghan, Victoria, Martin, Nicholas G, de Zubicaray, Greig I., Thompson, Paul M, McMahon, Katie L, Wright, Margaret J, Hansell, Narelle K, Strike, Lachlan T, van Eijk, Liza, O'Callaghan, Victoria, Martin, Nicholas G, de Zubicaray, Greig I., Thompson, Paul M, McMahon, Katie L, and Wright, Margaret J
Abstract: The hippocampus is a complex brain structure with key roles in cognitive and emotional processing and with subregion abnormalities associated with a range of disorders and psychopathologies. Here we combine data from two large independent young adult twin/sibling cohorts to obtain the most accurate estimates to date of genetic covariation between hippocampal subfield volumes and the hippocampus as a single volume. The combined sample included 2148 individuals, comprising 1073 individuals from 627 families (mean age = 22.3 years) from the Queensland Twin IMaging (QTIM) Study, and 1075 individuals from 454 families (mean age = 28.8 years) from the Human Connectome Project (HCP). Hippocampal subfields were segmented using FreeSurfer version 6.0 (CA4 and dentate gyrus were phenotypically and genetically indistinguishable and were summed to a single volume). Multivariate twin modeling was conducted in OpenMx to decompose variance into genetic and environmental sources. Bivariate analyses of hippocampal formation and each subfield volume showed that 10%-72% of subfield genetic variance was independent of the hippocampal formation, with greatest specificity found for the smaller volumes; for example, CA2/3 with 42% of genetic variance being independent of the hippocampus; fissure (63%); fimbria (72%); hippocampus-amygdala transition area (41%); parasubiculum (62%). In terms of genetic influence, whole hippocampal volume is a good proxy for the largest hippocampal subfields, but a poor substitute for the smaller subfields. Additive genetic sources accounted for 49%-77% of total variance for each of the subfields in the combined sample multivariate analysis. In addition, the multivariate analyses were sufficiently powered to identify common environmental influences (replicated in QTIM and HCP for the molecular layer and CA4/dentate gyrus, and accounting for 7%-16% of total variance for 8 of 10 subfields in the combined sample). This provides the clearest indication yet fr
Published: 2022

2. Persistence of Anxiety/Depression Symptoms in Early Adolescence: A Prospective Study of Daily Life Stress, Rumination, and Daytime Sleepiness in a Genetically Informative Cohort

Author: Hansell, Narelle K, Strike, Lachlan T, de Zubicaray, Greig I, Thompson, Paul M., McMahon, Katie L, Wright, Margaret J, Hansell, Narelle K, Strike, Lachlan T, de Zubicaray, Greig I, Thompson, Paul M., McMahon, Katie L, and Wright, Margaret J
Abstract: In this prospective study of mental health, we examine the influence of three interrelated traits - perceived stress, rumination, and daytime sleepiness - and their association with symptoms of anxiety and depression in early adolescence. Given the known associations between these traits, an important objective is to determine the extent to which they may independently predict anxiety/depression symptoms. Twin pairs from the Queensland Twin Adolescent Brain (QTAB) project were assessed on two occasions (N = 211 pairs aged 9-14 years at baseline and 152 pairs aged 10-16 years at follow-up). Linear regression models and quantitative genetic modeling were used to analyze the data. Prospectively, perceived stress, rumination, and daytime sleepiness accounted for 8-11% of the variation in later anxiety/depression; familial influences contributed strongly to these associations. However, only perceived stress significantly predicted change in anxiety/depression, accounting for 3% of variance at follow-up after adjusting for anxiety/depression at baseline, although it did not do so independently of rumination and daytime sleepiness. Bidirectional effects were found between all traits over time. These findings suggest an underlying architecture that is shared, to some degree, by all traits, while the literature points to hypothalamic-pituitary-adrenal (HPA) axis and/or circadian systems as potential sources of overlapping influence and possible avenues for intervention.
Published: 2022

3. Autism-related dietary preferences mediate autism-gut microbiome associations

Author: Yap, Chloe X, Henders, Anjali K, Alvares, Gail A, Wood, David L A, Krause, Lutz, Tyson, Gene W, Restuadi, Restuadi, Wallace, Leanne, McLaren, Tiana, Hansell, Narelle K, Cleary, Dominique, Grove, Rachel, Hafekost, Claire, Harun, Alexis, Holdsworth, Helen, Jellett, Rachel, Khan, Feroza, Lawson, Lauren P, Leslie, Jodie, Frenk, Mira Levis, Masi, Anne, Mathew, Nisha E, Muniandy, Melanie, Nothard, Michaela, Miller, Jessica L, Nunn, Lorelle, Holtmann, Gerald, Strike, Lachlan T, de Zubicaray, Greig I, Thompson, Paul M, McMahon, Katie L, Wright, Margaret J, Visscher, Peter M, Dawson, Paul A, Dissanayake, Cheryl, Eapen, Valsamma, Heussler, Helen S, McRae, Allan F, Whitehouse, Andrew J O, Wray, Naomi R, Gratten, Jacob, Yap, Chloe X, Henders, Anjali K, Alvares, Gail A, Wood, David L A, Krause, Lutz, Tyson, Gene W, Restuadi, Restuadi, Wallace, Leanne, McLaren, Tiana, Hansell, Narelle K, Cleary, Dominique, Grove, Rachel, Hafekost, Claire, Harun, Alexis, Holdsworth, Helen, Jellett, Rachel, Khan, Feroza, Lawson, Lauren P, Leslie, Jodie, Frenk, Mira Levis, Masi, Anne, Mathew, Nisha E, Muniandy, Melanie, Nothard, Michaela, Miller, Jessica L, Nunn, Lorelle, Holtmann, Gerald, Strike, Lachlan T, de Zubicaray, Greig I, Thompson, Paul M, McMahon, Katie L, Wright, Margaret J, Visscher, Peter M, Dawson, Paul A, Dissanayake, Cheryl, Eapen, Valsamma, Heussler, Helen S, McRae, Allan F, Whitehouse, Andrew J O, Wray, Naomi R, and Gratten, Jacob
Abstract: There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.
Published: 2021

4. Are Sex Differences in Human Brain Structure Associated With Sex Differences in Behavior?

Author: van Eijk, Liza, Zhu, Dajiang, Couvy-Duchesne, Baptiste, Strike, Lachlan T, Lee, Anthony J, Hansell, Narelle K, Thompson, Paul M, de Zubicaray, Greig I, McMahon, Katie L, Wright, Margaret J, Zietsch, Brendan P, van Eijk, Liza, Zhu, Dajiang, Couvy-Duchesne, Baptiste, Strike, Lachlan T, Lee, Anthony J, Hansell, Narelle K, Thompson, Paul M, de Zubicaray, Greig I, McMahon, Katie L, Wright, Margaret J, and Zietsch, Brendan P
Abstract: On average, men and women differ in brain structure and behavior, raising the possibility of a link between sex differences in brain and behavior. But women and men are also subject to different societal and cultural norms. We navigated this challenge by investigating variability of sex-differentiated brain structure within each sex. Using data from the Queensland Twin IMaging study (n = 1,040) and Human Connectome Project (n = 1,113), we obtained data-driven measures of individual differences along a male-female dimension for brain and behavior based on average sex differences in brain structure and behavior, respectively. We found a weak association between these brain and behavioral differences, driven by brain size. These brain and behavioral differences were moderately heritable. Our findings suggest that behavioral sex differences are, to some extent, related to sex differences in brain structure but that this is mainly driven by differences in brain size, and causality should be interpreted cautiously.
Published: 2021

5. The genetic architecture of the human cerebral cortex

Author: Grasby, Katrina L., Jahanshad, Neda, Painter, Jodie N., Colodro-Conde, Lucia, Bralten, Janita, Hibar, Derrek P., Lind, Penelope A., Pizzagalli, Fabrizio, Ching, Christopher R. K., McMahon, Mary Agnes B., Shatokhina, Natalia, Zsembik, Leo C. P., Thomopoulos, Sophia I., Zhu, Alyssa H., Strike, Lachlan T., Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio A. A., Alnaes, Dag, Amlien, Inge K., Andersson, Micael, Ard, Tyler, Armstrong, Nicola J., Ashley-Koch, Allison, Atkins, Joshua R., Bernard, Manon, Brouwer, Rachel M., Buimer, Elizabeth E. L., Bulow, Robin, Burger, Christian, Cannon, Dara M., Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W., Couvy-Duchesne, Baptiste, Dale, Anders M., Dalvie, Shareefa, de Araujo, Tania K., de Zubicaray, Greig I., de Zwarte, Sonja M. C., den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah-Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O., Foley, Sonya F., Ford, Judith M., Fukunaga, Masaki, Garrett, Melanie E., Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Gurholt, Tiril P., Gutman, Boris A., Hansell, Narelle K., Harris, Mathew A., Harrison, Marc B., Haswell, Courtney C., Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J., Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke-Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E., Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R., Kramer, Bernd, Lam, Max, Lancaster, Thomas M., Lee, Phil H., Lett, Tristram A., Lewis, Lindsay B., Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F., Mathias, Samuel R., Melzer, Tracy R., Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Moreira, Jose C. V., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Loohuis, Loes M. Olde, Orfanos, Dimitri Papadopoulos, Pearson, John F., Pitcher, Toni L., Putz, Benno, Quide, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M., Reay, William R., Redlich, Ronny, Reinbold, Celine S., Repple, Jonathan, Richard, Genevieve, Riedel, Brandalyn C., Risacher, Shannon L., Rocha, Cristiane S., Mota, Nina R., Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J., Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R., Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sonderby, Ida E., Sprooten, Emma, Tansey, Katherine E., Teumer, Alexander, Thalamuthu, Anbupalam, Tordesillas-Gutierrez, Diana, Turner, Jessica A., Uhlmann, Anne, Vallerga, Costanza L., van der Meer, Dennis, van Donkelaar, Marjolein M. J., van Eijk, Liza, van Erp, Theo G. M., van Haren, Neeltje E. M., van Rooij, Daan, van Tol, Marie-Jose, Veldink, Jan H., Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Witt, Stephanie H., Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L., Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P., Artiges, Eric, Assareh, Amelia A., Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L., Brown, Gregory G., Cichon, Sven, Curran, Joanne E., Davies, Gareth E., Degenhardt, Franziska, Dennis, Michelle F., Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P., Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A., Green, Robert C., Hausler, Alexander N., Heindel, Walter, Ho, Beng-Choon, Hoffmann, Wolfgang U., Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R., Jr., Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A., Kolskar, Knut, Koops, Sanne, Krug, Axel, Lim, Kelvin O., Luykx, Jurjen J., Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., Matthews, Sarah, Van Son, Jaqueline Mayoral, McEwen, Sarah C., Melle, Ingrid, Morris, Derek W., Mueller, Bryon A., Nauck, Matthias, Nordvik, Jan E., Noethen, Markus M., O'Leary, Daniel S., Opel, Nils, Martinot, Marie-Laure Paillere, Pike, G. Bruce, Preda, Adrian, Quinlan, Erin B., Rasser, Paul E., Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M., Tooney, Paul A., Torres, Fabio R., Veltman, Dick J., Voyvodic, James T., Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H. H., Bis, Joshua C., Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Ikram, M. Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L., Mazoyer, Bernard, Mosley, Thomas H., Roshchupkin, Gennady V., Satizabal, Claudia L., Schmidt, Reinhold, Seshadri, Sudha, Yang, Qiong, Alvim, Marina K. M., Ames, David, Anderson, Tim J., Andreassen, Ole A., Arias-Vasquez, Alejandro, Bastin, Mark E., Baune, Bernhard T., Beckham, Jean C., Blangero, John, Boomsma, Dorret I., Brodaty, Henry, Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bustillo, Juan R., Cahn, Wiepke, Cairns, Murray J., Calhoun, Vince, Carr, Vaughan J., Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L., Cendes, Fernando, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C., Dannlowski, Udo, de Geus, Eco J. C., Deary, Ian J., Delanty, Norman, Depondt, Chantal, Desrivieres, Sylvane, Donohoe, Gary, Espeseth, Thomas, Fernandez, Guillen, Fisher, Simon E., Flor, Herta, Forstner, Andreas J., Francks, Clyde, Franke, Barbara, Glahn, David C., Gollub, Randy L., Grabe, Hans J., Gruber, Oliver, Haberg, Asta K., Hariri, Ahmad R., Hartman, Catharina A., Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans A., Hillegers, Manon H. J., Hoekstra, Pieter J., Holmes, Avram J., Hong, L. Elliot, Hopkins, William D., Pol, Hilleke E. Hulshoff, Jernigan, Terry L., Jonsson, Erik G., Kahn, Rene S., Kennedy, Martin A., Kircher, Tilo T. J., Kochunov, Peter, Kwok, John B. J., Le Hellard, Stephanie, Loughland, Carmel M., Martin, Nicholas G., Martinot, Jean-Luc, McDonald, Colm, McMahon, Katie L., Meyer-Lindenberg, Andreas, Michie, Patricia T., Morey, Rajendra A., Mowry, Bryan, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A., Pantelis, Christos, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Polderman, Tinca J. C., Posthuma, Danielle, Rietschel, Marcella, Roffman, Joshua L., Rowland, Laura M., Sachdev, Perminder S., Samann, Philipp G., Schall, Ulrich, Schumann, Gunter, Scott, Rodney J., Sim, Kang, Sisodiya, Sanjay M., Smoller, Jordan W., Sommer, Iris E., St Pourcain, Beate, Stein, Dan J., Toga, Arthur W., Trollor, Julian N., Van der Wee, Nic J. A., van't Ent, Dennis, Volzke, Henry, Walter, Henrik, Weber, Bernd, Weinberger, Daniel R., Wright, Margaret J., Zhou, Juan, Stein, Jason L., Thompson, Paul M., Medland, Sarah E., Grasby, Katrina L., Jahanshad, Neda, Painter, Jodie N., Colodro-Conde, Lucia, Bralten, Janita, Hibar, Derrek P., Lind, Penelope A., Pizzagalli, Fabrizio, Ching, Christopher R. K., McMahon, Mary Agnes B., Shatokhina, Natalia, Zsembik, Leo C. P., Thomopoulos, Sophia I., Zhu, Alyssa H., Strike, Lachlan T., Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio A. A., Alnaes, Dag, Amlien, Inge K., Andersson, Micael, Ard, Tyler, Armstrong, Nicola J., Ashley-Koch, Allison, Atkins, Joshua R., Bernard, Manon, Brouwer, Rachel M., Buimer, Elizabeth E. L., Bulow, Robin, Burger, Christian, Cannon, Dara M., Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W., Couvy-Duchesne, Baptiste, Dale, Anders M., Dalvie, Shareefa, de Araujo, Tania K., de Zubicaray, Greig I., de Zwarte, Sonja M. C., den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah-Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O., Foley, Sonya F., Ford, Judith M., Fukunaga, Masaki, Garrett, Melanie E., Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Gurholt, Tiril P., Gutman, Boris A., Hansell, Narelle K., Harris, Mathew A., Harrison, Marc B., Haswell, Courtney C., Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J., Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke-Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E., Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R., Kramer, Bernd, Lam, Max, Lancaster, Thomas M., Lee, Phil H., Lett, Tristram A., Lewis, Lindsay B., Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F., Mathias, Samuel R., Melzer, Tracy R., Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Moreira, Jose C. V., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Loohuis, Loes M. Olde, Orfanos, Dimitri Papadopoulos, Pearson, John F., Pitcher, Toni L., Putz, Benno, Quide, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M., Reay, William R., Redlich, Ronny, Reinbold, Celine S., Repple, Jonathan, Richard, Genevieve, Riedel, Brandalyn C., Risacher, Shannon L., Rocha, Cristiane S., Mota, Nina R., Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J., Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R., Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sonderby, Ida E., Sprooten, Emma, Tansey, Katherine E., Teumer, Alexander, Thalamuthu, Anbupalam, Tordesillas-Gutierrez, Diana, Turner, Jessica A., Uhlmann, Anne, Vallerga, Costanza L., van der Meer, Dennis, van Donkelaar, Marjolein M. J., van Eijk, Liza, van Erp, Theo G. M., van Haren, Neeltje E. M., van Rooij, Daan, van Tol, Marie-Jose, Veldink, Jan H., Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Witt, Stephanie H., Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L., Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P., Artiges, Eric, Assareh, Amelia A., Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L., Brown, Gregory G., Cichon, Sven, Curran, Joanne E., Davies, Gareth E., Degenhardt, Franziska, Dennis, Michelle F., Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P., Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A., Green, Robert C., Hausler, Alexander N., Heindel, Walter, Ho, Beng-Choon, Hoffmann, Wolfgang U., Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R., Jr., Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A., Kolskar, Knut, Koops, Sanne, Krug, Axel, Lim, Kelvin O., Luykx, Jurjen J., Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., Matthews, Sarah, Van Son, Jaqueline Mayoral, McEwen, Sarah C., Melle, Ingrid, Morris, Derek W., Mueller, Bryon A., Nauck, Matthias, Nordvik, Jan E., Noethen, Markus M., O'Leary, Daniel S., Opel, Nils, Martinot, Marie-Laure Paillere, Pike, G. Bruce, Preda, Adrian, Quinlan, Erin B., Rasser, Paul E., Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M., Tooney, Paul A., Torres, Fabio R., Veltman, Dick J., Voyvodic, James T., Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H. H., Bis, Joshua C., Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Ikram, M. Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L., Mazoyer, Bernard, Mosley, Thomas H., Roshchupkin, Gennady V., Satizabal, Claudia L., Schmidt, Reinhold, Seshadri, Sudha, Yang, Qiong, Alvim, Marina K. M., Ames, David, Anderson, Tim J., Andreassen, Ole A., Arias-Vasquez, Alejandro, Bastin, Mark E., Baune, Bernhard T., Beckham, Jean C., Blangero, John, Boomsma, Dorret I., Brodaty, Henry, Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bustillo, Juan R., Cahn, Wiepke, Cairns, Murray J., Calhoun, Vince, Carr, Vaughan J., Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L., Cendes, Fernando, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C., Dannlowski, Udo, de Geus, Eco J. C., Deary, Ian J., Delanty, Norman, Depondt, Chantal, Desrivieres, Sylvane, Donohoe, Gary, Espeseth, Thomas, Fernandez, Guillen, Fisher, Simon E., Flor, Herta, Forstner, Andreas J., Francks, Clyde, Franke, Barbara, Glahn, David C., Gollub, Randy L., Grabe, Hans J., Gruber, Oliver, Haberg, Asta K., Hariri, Ahmad R., Hartman, Catharina A., Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans A., Hillegers, Manon H. J., Hoekstra, Pieter J., Holmes, Avram J., Hong, L. Elliot, Hopkins, William D., Pol, Hilleke E. Hulshoff, Jernigan, Terry L., Jonsson, Erik G., Kahn, Rene S., Kennedy, Martin A., Kircher, Tilo T. J., Kochunov, Peter, Kwok, John B. J., Le Hellard, Stephanie, Loughland, Carmel M., Martin, Nicholas G., Martinot, Jean-Luc, McDonald, Colm, McMahon, Katie L., Meyer-Lindenberg, Andreas, Michie, Patricia T., Morey, Rajendra A., Mowry, Bryan, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A., Pantelis, Christos, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Polderman, Tinca J. C., Posthuma, Danielle, Rietschel, Marcella, Roffman, Joshua L., Rowland, Laura M., Sachdev, Perminder S., Samann, Philipp G., Schall, Ulrich, Schumann, Gunter, Scott, Rodney J., Sim, Kang, Sisodiya, Sanjay M., Smoller, Jordan W., Sommer, Iris E., St Pourcain, Beate, Stein, Dan J., Toga, Arthur W., Trollor, Julian N., Van der Wee, Nic J. A., van't Ent, Dennis, Volzke, Henry, Walter, Henrik, Weber, Bernd, Weinberger, Daniel R., Wright, Margaret J., Zhou, Juan, Stein, Jason L., Thompson, Paul M., and Medland, Sarah E.
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
Published: 2020
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6. The genetic architecture of the human cerebral cortex

Author: Grasby, Katrina L., Jahanshad, Neda, Painter, Jodie N., Colodro-Conde, Lucía, Bralten, Janita, Hibar, Derrek P., Lind, Penelope A., Pizzagalli, Fabrizio, Ching, Christopher R.K., McMahon, Mary Agnes B., Shatokhina, Natalia, Zsembik, Leo C.P., Thomopoulos, Sophia I., Zhu, Alyssa H., Strike, Lachlan T., Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio A.A., Alnæs, Dag, Amlien, Inge K., Andersson, Micael, Ard, Tyler, Armstrong, Nicola J., Ashley-Koch, Allison, Atkins, Joshua R., Bernard, Manon, Brouwer, Rachel M., Buimer, Elizabeth E.L., Bülow, Robin, Bürger, Christian, Cannon, Dara M., Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W., Couvy-Duchesne, Baptiste, Dale, Anders M., Dalvie, Shareefa, de Araujo, Tânia K., de Zubicaray, Greig I., de Zwarte, Sonja M.C., den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O., Foley, Sonya F., Ford, Judith M., Fukunaga, Masaki, Garrett, Melanie E., Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Gurholt, Tiril P., Gutman, Boris A., Hansell, Narelle K., Harris, Mathew A., Harrison, Marc B., Haswell, Courtney C., Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J., Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E., Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R., Krämer, Bernd, Lam, Max, Lancaster, Thomas M., Lee, Phil H., Lett, Tristram A., Lewis, Lindsay B., Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F., Mathias, Samuel R., Melzer, Tracy R., Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Moreira, Jose C.V., Mühleisen, Thomas W., Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M., Orfanos, Dimitri Papadopoulos, Pearson, John F., Pitcher, Toni L., Pütz, Benno, Quidé, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M., Reay, William R., Redlich, Ronny, Reinbold, Céline S., Repple, Jonathan, Richard, Geneviève, Riedel, Brandalyn C., Risacher, Shannon L., Rocha, Cristiane S., Mota, Nina R., Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J., Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R., Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E., Sprooten, Emma, Tansey, Katherine E., Teumer, Alexander, Thalamuthu, Anbupalam, Tordesillas-Gutiérrez, Diana, Turner, Jessica A., Uhlmann, Anne, Vallerga, Costanza L., van der Meer, Dennis, van Donkelaar, Marjolein M.J., van Eijk, Liza, van Erp, Theo G.M., van Haren, Neeltje E.M., van Rooij, Daan, van Tol, Marie José, Veldink, Jan H., Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Witt, Stephanie H., Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L., Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P., Artiges, Eric, Assareh, Amelia A., Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L., Brown, Gregory G., Cichon, Sven, Curran, Joanne E., Davies, Gareth E., Degenhardt, Franziska, Dennis, Michelle F., Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P., Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A., Green, Robert C., Häusler, Alexander N., Heindel, Walter, Ho, Beng Choon, Hoffmann, Wolfgang U., Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R., Jang, Mi Hyun, Jansen, Andreas, Kimbrel, Nathan A., Kolskår, Knut, Koops, Sanne, Krug, Axel, Lim, Kelvin O., Luykx, Jurjen J., Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., Matthews, Sarah, van Son, Jaqueline Mayoral, McEwen, Sarah C., Melle, Ingrid, Morris, Derek W., Mueller, Bryon A., Nauck, Matthias, Nordvik, Jan E., Nöthen, Markus M., O'Leary, Daniel S., Opel, Nils, Martinot, Marie Laure Paillère, Bruce Pike, G., Preda, Adrian, Quinlan, Erin B., Rasser, Paul E., Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M., Tooney, Paul A., Torres, Fábio R., Veltman, Dick J., Voyvodic, James T., Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H.H., Bis, Joshua C., Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Arfan Ikram, M., Launer, Lenore, Longstreth, W. T., Lopez, Oscar L., Fisher, Simon E., Martin, Nicholas G., McMahon, Katie L., Wright, Margaret J., Thompson, Paul M., Medland, Sarah E., Grasby, Katrina L., Jahanshad, Neda, Painter, Jodie N., Colodro-Conde, Lucía, Bralten, Janita, Hibar, Derrek P., Lind, Penelope A., Pizzagalli, Fabrizio, Ching, Christopher R.K., McMahon, Mary Agnes B., Shatokhina, Natalia, Zsembik, Leo C.P., Thomopoulos, Sophia I., Zhu, Alyssa H., Strike, Lachlan T., Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio A.A., Alnæs, Dag, Amlien, Inge K., Andersson, Micael, Ard, Tyler, Armstrong, Nicola J., Ashley-Koch, Allison, Atkins, Joshua R., Bernard, Manon, Brouwer, Rachel M., Buimer, Elizabeth E.L., Bülow, Robin, Bürger, Christian, Cannon, Dara M., Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W., Couvy-Duchesne, Baptiste, Dale, Anders M., Dalvie, Shareefa, de Araujo, Tânia K., de Zubicaray, Greig I., de Zwarte, Sonja M.C., den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O., Foley, Sonya F., Ford, Judith M., Fukunaga, Masaki, Garrett, Melanie E., Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Gurholt, Tiril P., Gutman, Boris A., Hansell, Narelle K., Harris, Mathew A., Harrison, Marc B., Haswell, Courtney C., Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J., Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E., Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R., Krämer, Bernd, Lam, Max, Lancaster, Thomas M., Lee, Phil H., Lett, Tristram A., Lewis, Lindsay B., Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F., Mathias, Samuel R., Melzer, Tracy R., Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Moreira, Jose C.V., Mühleisen, Thomas W., Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M., Orfanos, Dimitri Papadopoulos, Pearson, John F., Pitcher, Toni L., Pütz, Benno, Quidé, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M., Reay, William R., Redlich, Ronny, Reinbold, Céline S., Repple, Jonathan, Richard, Geneviève, Riedel, Brandalyn C., Risacher, Shannon L., Rocha, Cristiane S., Mota, Nina R., Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J., Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R., Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E., Sprooten, Emma, Tansey, Katherine E., Teumer, Alexander, Thalamuthu, Anbupalam, Tordesillas-Gutiérrez, Diana, Turner, Jessica A., Uhlmann, Anne, Vallerga, Costanza L., van der Meer, Dennis, van Donkelaar, Marjolein M.J., van Eijk, Liza, van Erp, Theo G.M., van Haren, Neeltje E.M., van Rooij, Daan, van Tol, Marie José, Veldink, Jan H., Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Witt, Stephanie H., Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L., Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P., Artiges, Eric, Assareh, Amelia A., Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L., Brown, Gregory G., Cichon, Sven, Curran, Joanne E., Davies, Gareth E., Degenhardt, Franziska, Dennis, Michelle F., Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P., Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A., Green, Robert C., Häusler, Alexander N., Heindel, Walter, Ho, Beng Choon, Hoffmann, Wolfgang U., Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R., Jang, Mi Hyun, Jansen, Andreas, Kimbrel, Nathan A., Kolskår, Knut, Koops, Sanne, Krug, Axel, Lim, Kelvin O., Luykx, Jurjen J., Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., Matthews, Sarah, van Son, Jaqueline Mayoral, McEwen, Sarah C., Melle, Ingrid, Morris, Derek W., Mueller, Bryon A., Nauck, Matthias, Nordvik, Jan E., Nöthen, Markus M., O'Leary, Daniel S., Opel, Nils, Martinot, Marie Laure Paillère, Bruce Pike, G., Preda, Adrian, Quinlan, Erin B., Rasser, Paul E., Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M., Tooney, Paul A., Torres, Fábio R., Veltman, Dick J., Voyvodic, James T., Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H.H., Bis, Joshua C., Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Arfan Ikram, M., Launer, Lenore, Longstreth, W. T., Lopez, Oscar L., Fisher, Simon E., Martin, Nicholas G., McMahon, Katie L., Wright, Margaret J., Thompson, Paul M., and Medland, Sarah E.
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
Published: 2020

7. Region-specific sex differences in the hippocampus

Author: van Eijk, Liza, Hansell, Narelle K., Strike, Lachlan T., Couvy-Duchesne, Baptiste, de Zubicaray, Greig I., Thompson, Paul M., McMahon, Katie L., Zietsch, Brendan P., Wright, Margaret J., van Eijk, Liza, Hansell, Narelle K., Strike, Lachlan T., Couvy-Duchesne, Baptiste, de Zubicaray, Greig I., Thompson, Paul M., McMahon, Katie L., Zietsch, Brendan P., and Wright, Margaret J.
Abstract: The hippocampus is a brain region critical for learning and memory, and is also implicated in several neuropsychiatric disorders that show sex differences in prevalence, symptom expression, and mean age of onset. On average, males have larger hippocampal volumes than females, but findings are inconclusive after adjusting for overall brain size. Although the hippocampus is a heterogenous structure, few studies have focused on sex differences in the hippocampal subfields – with little consensus on whether there are regionally specific sex differences in the hippocampus after adjusting for brain size, or whether it is important to adjust for total hippocampal volume (HPV). Here, using two young adult cohorts from the Queensland Twin IMaging study (QTIM; N = 727) and the Human Connectome Project (HCP; N = 960), we examined differences between males and females in the volumes of 12 hippocampal subfields, extracted using FreeSurfer 6.0. After adjusting the subfield volumes for either HPV or brain size (brain segmentation volume (BSV)) using four controlling methods (allometric, covariate, residual and matching), we estimated the percentage difference of the sex effect (males versus females) and Cohen's d using hierarchical general linear models. Males had larger volumes compared to females in the parasubiculum (up to 6.04%; Cohen's d = 0.46) and fimbria (up to 8.75%; d = 0.54) after adjusting for HPV. These sex differences were robust across the two cohorts and multiple controlling methods, though within cohort effect sizes were larger for the matched approach, due to the smaller sub-sample. Additional sex effects were identified in the HCP cohort and combined (QTIM and HCP) sample (hippocampal fissure (up to 6.79%), presubiculum (up to 3.08%), and hippocampal tail (up to −0.23%)). In contrast, no sex differences were detected for the volume of the cornu ammonis (CA)2/3, CA4, Hippocampus-Amygdala Transition Area (HATA), or the granule cell layer of the dentate
Published: 2020

8. The genetic architecture of the human cerebral cortex.

Author: Grasby, Katrina L, Grasby, Katrina L, Jahanshad, Neda, Painter, Jodie N, Colodro-Conde, Lucía, Bralten, Janita, Hibar, Derrek P, Lind, Penelope A, Pizzagalli, Fabrizio, Ching, Christopher RK, McMahon, Mary Agnes B, Shatokhina, Natalia, Zsembik, Leo CP, Thomopoulos, Sophia I, Zhu, Alyssa H, Strike, Lachlan T, Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio AA, Alnæs, Dag, Amlien, Inge K, Andersson, Micael, Ard, Tyler, Armstrong, Nicola J, Ashley-Koch, Allison, Atkins, Joshua R, Bernard, Manon, Brouwer, Rachel M, Buimer, Elizabeth EL, Bülow, Robin, Bürger, Christian, Cannon, Dara M, Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W, Couvy-Duchesne, Baptiste, Dale, Anders M, Dalvie, Shareefa, de Araujo, Tânia K, de Zubicaray, Greig I, de Zwarte, Sonja MC, den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah-Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O, Foley, Sonya F, Ford, Judith M, Fukunaga, Masaki, Garrett, Melanie E, Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L, Green, Melissa J, Groenewold, Nynke A, Grotegerd, Dominik, Gurholt, Tiril P, Gutman, Boris A, Hansell, Narelle K, Harris, Mathew A, Harrison, Marc B, Haswell, Courtney C, Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J, Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke-Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E, Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R, Krämer, Bernd, Lam, Max, Lancaster, Thomas M, Lee, Phil H, Lett, Tristram A, Lewis, Lindsay B, Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F, Mathias, Samuel R, Melzer, Tracy R, Milaneschi, Yuri, Grasby, Katrina L, Grasby, Katrina L, Jahanshad, Neda, Painter, Jodie N, Colodro-Conde, Lucía, Bralten, Janita, Hibar, Derrek P, Lind, Penelope A, Pizzagalli, Fabrizio, Ching, Christopher RK, McMahon, Mary Agnes B, Shatokhina, Natalia, Zsembik, Leo CP, Thomopoulos, Sophia I, Zhu, Alyssa H, Strike, Lachlan T, Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio AA, Alnæs, Dag, Amlien, Inge K, Andersson, Micael, Ard, Tyler, Armstrong, Nicola J, Ashley-Koch, Allison, Atkins, Joshua R, Bernard, Manon, Brouwer, Rachel M, Buimer, Elizabeth EL, Bülow, Robin, Bürger, Christian, Cannon, Dara M, Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W, Couvy-Duchesne, Baptiste, Dale, Anders M, Dalvie, Shareefa, de Araujo, Tânia K, de Zubicaray, Greig I, de Zwarte, Sonja MC, den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah-Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O, Foley, Sonya F, Ford, Judith M, Fukunaga, Masaki, Garrett, Melanie E, Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L, Green, Melissa J, Groenewold, Nynke A, Grotegerd, Dominik, Gurholt, Tiril P, Gutman, Boris A, Hansell, Narelle K, Harris, Mathew A, Harrison, Marc B, Haswell, Courtney C, Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J, Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke-Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E, Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R, Krämer, Bernd, Lam, Max, Lancaster, Thomas M, Lee, Phil H, Lett, Tristram A, Lewis, Lindsay B, Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F, Mathias, Samuel R, Melzer, Tracy R, and Milaneschi, Yuri
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
Published: 2020

9. Genetic architecture of subcortical brain structures in 38,851 individuals

Author: Satizabal, Claudia L., Adams, Hieab H. H., Hibar, Derrek P., White, Charles C., Knol, Maria J., Stein, Jason L., Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady, V, Smith, Albert, V, Bis, Joshua C., Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J., Yang, Jingyun, Yanek, Lisa R., Lee, Tom, V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D., Desrivieres, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentera, Miguel E., Kim, Sungeun, Hoehn, David, Armstrong, Nicola J., Chen, Qiang, Holmes, Avram J., den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santianez, Roberto, Kraemer, Bernd, Haberg, Asta K., Jones, Hannah J., Pike, G. Bruce, Stein, Dan J., Stevens, Allison, Bralten, Janita, Vernooij, Meike W., Harris, Tamara B., Filippi, Irina, Witte, A. Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H., Becker, James T., Doan, Nhat Trung, Hagenaars, Saskia P., Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M., Ames, David, Goldman, Aaron L., Lee, Phil H., Boomsma, Dorret, I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M., Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M., Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E., Shin, Jean, Ipser, Jonathan C., Vinke, Louis N., Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K., Aribisala, Benjamin S., Schmidt, Helena, Strike, Lachlan T., Cheng, Ching-Yu, Risacher, Shannon L., Puetz, Benno, Fleischman, Debra A., Assareh, Amelia A., Mattay, Venkata S., Buckner, Randy L., Mecocci, Patrizia, Dale, Anders M., Cichon, Sven, Boks, Marco P., Matarin, Mar, Penninx, Brenda W. J. H., Calhoun, Vince D., Chakravarty, M. Mallar, Marquand, Andre F., Macare, Christine, Masouleh, Shahrzad Kharabian, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome, I, Schork, Andrew J., Liewald, David C. M., de Zubicaray, Greig, I, Wong, Tien Yin, Shen, Li, Saemann, Philipp G., Brodaty, Henry, Roffman, Joshua L., de Geus, Eco J. C., Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R., Cavalleri, Gianpiero L., van der Wee, Nic J. A., McIntosh, Andrew M., Gollub, Randy L., Bulayeva, Kazima B., Bernard, Manon, Richards, Jennifer S., Himali, Jayandra J., Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T., Hernandez, Maria C. Valdes, Hansell, Narelle K., van Erp, Theo G. M., Wolf, Christiane, Kwok, John B. J., Vellas, Bruno, Heinz, Andreas, Loohuis, Loes M. Olde, Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R. K., Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M., Bastin, Mark E., Montgomery, Grant W., Foroud, Tatiana M., Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D., van Donkelaar, Marjolein M. J., Yang, Qiong, Hosten, Norbert, Green, Robert C., Thalamuthu, Anbupalam, Mohnke, Sebastian, Pol, Hilleke E. Hulshoff, Lin, Honghuang, Jack, Clifford R., Jr., Schofield, Peter R., Muehleisen, Thomas W., Maillard, Pauline, Potkin, Steven G., Wen, Wei, Fletcher, Evan, Toga, Arthur W., Gruber, Oliver, Huentelman, Matthew, Smith, George Davey, Launer, Lenore J., Nyberg, Lars, Jonsson, Erik G., Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N., Uitterlinden, Andre G., Weinberger, Daniel R., Steen, Vidar M., Fedko, Iryna O., Groenewold, Nynke A., Niessen, Wiro J., Toro, Roberto, Tzourio, Christophe, Longstreth, William T., Jr., Ikram, M. Kamran, Smoller, Jordan W., van Tol, Marie-Jose, Sussmann, Jessika E., Paus, Tomas, Lemaitre, Herve, Schroeter, Matthias L., Mazoyer, Bernard, Andreassen, Ole A., Holsboer, Florian, Depondt, Chantal, Veltman, Dick J., Turner, Jessica A., Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J., McMahon, Katie L., Mueller-Myhsok, Bertram, Brouwer, Rachel M., Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H., Cheung, Joshua W., Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P., Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G., Kanai, Ryota, Westman, Eric, Kahn, Rene S., Sisodiya, Sanjay M., White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G., Voelzke, Henry, Wright, Margaret J., van't Ent, Dennis, Noethen, Markus M., Ophoff, Roel A., Buitelaar, Jan K., Fernandez, Guilln, Sachdev, Perminder S., Rietschel, Marcella, van Haren, Neeltje E. M., Fisher, Simon E., Beiser, Alexa S., Francks, Clyde, Saykin, Andrew J., Mather, Karen A., Romanczuk-Seiferth, Nina, Hartman, Catharina A., DeStefano, Anita L., Heslenfeld, Dirk J., Weiner, Michael W., Walter, Henrik, Hoekstra, Pieter J., Nyquist, Paul A., Franke, Barbara, Bennett, David A., Grabe, Hans J., Johnson, Andrew D., Chen, Christopher, van Duijn, Cornelia M., Lopez, Oscar L., Fornage, Myriam, Wardlaw, Joanna M., Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L., Villringer, Arno, Debette, Stephanie, Gudnason, Vilmundur, Medland, Sarah E., Shulman, Joshua M., Thompson, Paul M., Seshadri, Sudha, Ikram, M. Arfan, Satizabal, Claudia L., Adams, Hieab H. H., Hibar, Derrek P., White, Charles C., Knol, Maria J., Stein, Jason L., Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady, V, Smith, Albert, V, Bis, Joshua C., Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J., Yang, Jingyun, Yanek, Lisa R., Lee, Tom, V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D., Desrivieres, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentera, Miguel E., Kim, Sungeun, Hoehn, David, Armstrong, Nicola J., Chen, Qiang, Holmes, Avram J., den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santianez, Roberto, Kraemer, Bernd, Haberg, Asta K., Jones, Hannah J., Pike, G. Bruce, Stein, Dan J., Stevens, Allison, Bralten, Janita, Vernooij, Meike W., Harris, Tamara B., Filippi, Irina, Witte, A. Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H., Becker, James T., Doan, Nhat Trung, Hagenaars, Saskia P., Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M., Ames, David, Goldman, Aaron L., Lee, Phil H., Boomsma, Dorret, I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M., Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M., Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E., Shin, Jean, Ipser, Jonathan C., Vinke, Louis N., Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K., Aribisala, Benjamin S., Schmidt, Helena, Strike, Lachlan T., Cheng, Ching-Yu, Risacher, Shannon L., Puetz, Benno, Fleischman, Debra A., Assareh, Amelia A., Mattay, Venkata S., Buckner, Randy L., Mecocci, Patrizia, Dale, Anders M., Cichon, Sven, Boks, Marco P., Matarin, Mar, Penninx, Brenda W. J. H., Calhoun, Vince D., Chakravarty, M. Mallar, Marquand, Andre F., Macare, Christine, Masouleh, Shahrzad Kharabian, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome, I, Schork, Andrew J., Liewald, David C. M., de Zubicaray, Greig, I, Wong, Tien Yin, Shen, Li, Saemann, Philipp G., Brodaty, Henry, Roffman, Joshua L., de Geus, Eco J. C., Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R., Cavalleri, Gianpiero L., van der Wee, Nic J. A., McIntosh, Andrew M., Gollub, Randy L., Bulayeva, Kazima B., Bernard, Manon, Richards, Jennifer S., Himali, Jayandra J., Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T., Hernandez, Maria C. Valdes, Hansell, Narelle K., van Erp, Theo G. M., Wolf, Christiane, Kwok, John B. J., Vellas, Bruno, Heinz, Andreas, Loohuis, Loes M. Olde, Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R. K., Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M., Bastin, Mark E., Montgomery, Grant W., Foroud, Tatiana M., Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D., van Donkelaar, Marjolein M. J., Yang, Qiong, Hosten, Norbert, Green, Robert C., Thalamuthu, Anbupalam, Mohnke, Sebastian, Pol, Hilleke E. Hulshoff, Lin, Honghuang, Jack, Clifford R., Jr., Schofield, Peter R., Muehleisen, Thomas W., Maillard, Pauline, Potkin, Steven G., Wen, Wei, Fletcher, Evan, Toga, Arthur W., Gruber, Oliver, Huentelman, Matthew, Smith, George Davey, Launer, Lenore J., Nyberg, Lars, Jonsson, Erik G., Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N., Uitterlinden, Andre G., Weinberger, Daniel R., Steen, Vidar M., Fedko, Iryna O., Groenewold, Nynke A., Niessen, Wiro J., Toro, Roberto, Tzourio, Christophe, Longstreth, William T., Jr., Ikram, M. Kamran, Smoller, Jordan W., van Tol, Marie-Jose, Sussmann, Jessika E., Paus, Tomas, Lemaitre, Herve, Schroeter, Matthias L., Mazoyer, Bernard, Andreassen, Ole A., Holsboer, Florian, Depondt, Chantal, Veltman, Dick J., Turner, Jessica A., Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J., McMahon, Katie L., Mueller-Myhsok, Bertram, Brouwer, Rachel M., Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H., Cheung, Joshua W., Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P., Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G., Kanai, Ryota, Westman, Eric, Kahn, Rene S., Sisodiya, Sanjay M., White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G., Voelzke, Henry, Wright, Margaret J., van't Ent, Dennis, Noethen, Markus M., Ophoff, Roel A., Buitelaar, Jan K., Fernandez, Guilln, Sachdev, Perminder S., Rietschel, Marcella, van Haren, Neeltje E. M., Fisher, Simon E., Beiser, Alexa S., Francks, Clyde, Saykin, Andrew J., Mather, Karen A., Romanczuk-Seiferth, Nina, Hartman, Catharina A., DeStefano, Anita L., Heslenfeld, Dirk J., Weiner, Michael W., Walter, Henrik, Hoekstra, Pieter J., Nyquist, Paul A., Franke, Barbara, Bennett, David A., Grabe, Hans J., Johnson, Andrew D., Chen, Christopher, van Duijn, Cornelia M., Lopez, Oscar L., Fornage, Myriam, Wardlaw, Joanna M., Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L., Villringer, Arno, Debette, Stephanie, Gudnason, Vilmundur, Medland, Sarah E., Shulman, Joshua M., Thompson, Paul M., Seshadri, Sudha, and Ikram, M. Arfan
Abstract: Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Published: 2019
Full Text: View/download PDF

10. Genetic architecture of subcortical brain structures in 38,851 individuals

Author: Satizabal, Claudia L., Adams, Hieab H. H., Hibar, Derrek P., White, Charles C., Knol, Maria J., Stein, Jason L., Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady, V, Smith, Albert, V, Bis, Joshua C., Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J., Yang, Jingyun, Yanek, Lisa R., Lee, Tom, V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D., Desrivieres, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentera, Miguel E., Kim, Sungeun, Hoehn, David, Armstrong, Nicola J., Chen, Qiang, Holmes, Avram J., den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santianez, Roberto, Kraemer, Bernd, Håberg, Asta K., Jones, Hannah J., Pike, G. Bruce, Stein, Dan J., Stevens, Allison, Bralten, Janita, Vernooij, Meike W., Harris, Tamara B., Filippi, Irina, Witte, A. Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H., Becker, James T., Doan, Nhat Trung, Hagenaars, Saskia P., Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M., Ames, David, Goldman, Aaron L., Lee, Phil H., Boomsma, Dorret, I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M., Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M., Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E., Shin, Jean, Ipser, Jonathan C., Vinke, Louis N., Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K., Aribisala, Benjamin S., Schmidt, Helena, Strike, Lachlan T., Cheng, Ching-Yu, Risacher, Shannon L., Puetz, Benno, Fleischman, Debra A., Assareh, Amelia A., Mattay, Venkata S., Buckner, Randy L., Mecocci, Patrizia, Dale, Anders M., Cichon, Sven, Boks, Marco P., Matarin, Mar, Penninx, Brenda W. J. H., Calhoun, Vince D., Chakravarty, M. Mallar, Marquand, Andre F., Macare, Christine, Masouleh, Shahrzad Kharabian, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome, I, Schork, Andrew J., Liewald, David C. M., de Zubicaray, Greig, I, Wong, Tien Yin, Shen, Li, Saemann, Philipp G., Brodaty, Henry, Roffman, Joshua L., de Geus, Eco J. C., Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R., Cavalleri, Gianpiero L., van der Wee, Nic J. A., McIntosh, Andrew M., Gollub, Randy L., Bulayeva, Kazima B., Bernard, Manon, Richards, Jennifer S., Himali, Jayandra J., Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T., Hernandez, Maria C. Valdes, Hansell, Narelle K., van Erp, Theo G. M., Wolf, Christiane, Kwok, John B. J., Vellas, Bruno, Heinz, Andreas, Loohuis, Loes M. Olde, Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R. K., Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M., Bastin, Mark E., Montgomery, Grant W., Foroud, Tatiana M., Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D., van Donkelaar, Marjolein M. J., Yang, Qiong, Hosten, Norbert, Green, Robert C., Thalamuthu, Anbupalam, Mohnke, Sebastian, Pol, Hilleke E. Hulshoff, Lin, Honghuang, Jack, Clifford R., Jr., Schofield, Peter R., Muehleisen, Thomas W., Maillard, Pauline, Potkin, Steven G., Wen, Wei, Fletcher, Evan, Toga, Arthur W., Gruber, Oliver, Huentelman, Matthew, Smith, George Davey, Launer, Lenore J., Nyberg, Lars, Jönsson, Erik G., Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N., Uitterlinden, Andre G., Weinberger, Daniel R., Steen, Vidar M., Fedko, Iryna O., Groenewold, Nynke A., Niessen, Wiro J., Toro, Roberto, Tzourio, Christophe, Longstreth, William T., Jr., Ikram, M. Kamran, Smoller, Jordan W., van Tol, Marie-Jose, Sussmann, Jessika E., Paus, Tomas, Lemaitre, Herve, Schroeter, Matthias L., Mazoyer, Bernard, Andreassen, Ole A., Holsboer, Florian, Depondt, Chantal, Veltman, Dick J., Turner, Jessica A., Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J., McMahon, Katie L., Mueller-Myhsok, Bertram, Brouwer, Rachel M., Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H., Cheung, Joshua W., Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P., Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G., Kanai, Ryota, Westman, Eric, Kahn, Rene S., Sisodiya, Sanjay M., White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G., Voelzke, Henry, Wright, Margaret J., van't Ent, Dennis, Noethen, Markus M., Ophoff, Roel A., Buitelaar, Jan K., Fernandez, Guilln, Sachdev, Perminder S., Rietschel, Marcella, van Haren, Neeltje E. M., Fisher, Simon E., Beiser, Alexa S., Francks, Clyde, Saykin, Andrew J., Mather, Karen A., Romanczuk-Seiferth, Nina, Hartman, Catharina A., DeStefano, Anita L., Heslenfeld, Dirk J., Weiner, Michael W., Walter, Henrik, Hoekstra, Pieter J., Nyquist, Paul A., Franke, Barbara, Bennett, David A., Grabe, Hans J., Johnson, Andrew D., Chen, Christopher, van Duijn, Cornelia M., Lopez, Oscar L., Fornage, Myriam, Wardlaw, Joanna M., Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L., Villringer, Arno, Debette, Stephanie, Gudnason, Vilmundur, Medland, Sarah E., Shulman, Joshua M., Thompson, Paul M., Seshadri, Sudha, Ikram, M. Arfan, Satizabal, Claudia L., Adams, Hieab H. H., Hibar, Derrek P., White, Charles C., Knol, Maria J., Stein, Jason L., Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady, V, Smith, Albert, V, Bis, Joshua C., Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J., Yang, Jingyun, Yanek, Lisa R., Lee, Tom, V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D., Desrivieres, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentera, Miguel E., Kim, Sungeun, Hoehn, David, Armstrong, Nicola J., Chen, Qiang, Holmes, Avram J., den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santianez, Roberto, Kraemer, Bernd, Håberg, Asta K., Jones, Hannah J., Pike, G. Bruce, Stein, Dan J., Stevens, Allison, Bralten, Janita, Vernooij, Meike W., Harris, Tamara B., Filippi, Irina, Witte, A. Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H., Becker, James T., Doan, Nhat Trung, Hagenaars, Saskia P., Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M., Ames, David, Goldman, Aaron L., Lee, Phil H., Boomsma, Dorret, I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M., Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M., Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E., Shin, Jean, Ipser, Jonathan C., Vinke, Louis N., Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K., Aribisala, Benjamin S., Schmidt, Helena, Strike, Lachlan T., Cheng, Ching-Yu, Risacher, Shannon L., Puetz, Benno, Fleischman, Debra A., Assareh, Amelia A., Mattay, Venkata S., Buckner, Randy L., Mecocci, Patrizia, Dale, Anders M., Cichon, Sven, Boks, Marco P., Matarin, Mar, Penninx, Brenda W. J. H., Calhoun, Vince D., Chakravarty, M. Mallar, Marquand, Andre F., Macare, Christine, Masouleh, Shahrzad Kharabian, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome, I, Schork, Andrew J., Liewald, David C. M., de Zubicaray, Greig, I, Wong, Tien Yin, Shen, Li, Saemann, Philipp G., Brodaty, Henry, Roffman, Joshua L., de Geus, Eco J. C., Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R., Cavalleri, Gianpiero L., van der Wee, Nic J. A., McIntosh, Andrew M., Gollub, Randy L., Bulayeva, Kazima B., Bernard, Manon, Richards, Jennifer S., Himali, Jayandra J., Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T., Hernandez, Maria C. Valdes, Hansell, Narelle K., van Erp, Theo G. M., Wolf, Christiane, Kwok, John B. J., Vellas, Bruno, Heinz, Andreas, Loohuis, Loes M. Olde, Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R. K., Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M., Bastin, Mark E., Montgomery, Grant W., Foroud, Tatiana M., Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D., van Donkelaar, Marjolein M. J., Yang, Qiong, Hosten, Norbert, Green, Robert C., Thalamuthu, Anbupalam, Mohnke, Sebastian, Pol, Hilleke E. Hulshoff, Lin, Honghuang, Jack, Clifford R., Jr., Schofield, Peter R., Muehleisen, Thomas W., Maillard, Pauline, Potkin, Steven G., Wen, Wei, Fletcher, Evan, Toga, Arthur W., Gruber, Oliver, Huentelman, Matthew, Smith, George Davey, Launer, Lenore J., Nyberg, Lars, Jönsson, Erik G., Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N., Uitterlinden, Andre G., Weinberger, Daniel R., Steen, Vidar M., Fedko, Iryna O., Groenewold, Nynke A., Niessen, Wiro J., Toro, Roberto, Tzourio, Christophe, Longstreth, William T., Jr., Ikram, M. Kamran, Smoller, Jordan W., van Tol, Marie-Jose, Sussmann, Jessika E., Paus, Tomas, Lemaitre, Herve, Schroeter, Matthias L., Mazoyer, Bernard, Andreassen, Ole A., Holsboer, Florian, Depondt, Chantal, Veltman, Dick J., Turner, Jessica A., Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J., McMahon, Katie L., Mueller-Myhsok, Bertram, Brouwer, Rachel M., Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H., Cheung, Joshua W., Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P., Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G., Kanai, Ryota, Westman, Eric, Kahn, Rene S., Sisodiya, Sanjay M., White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G., Voelzke, Henry, Wright, Margaret J., van't Ent, Dennis, Noethen, Markus M., Ophoff, Roel A., Buitelaar, Jan K., Fernandez, Guilln, Sachdev, Perminder S., Rietschel, Marcella, van Haren, Neeltje E. M., Fisher, Simon E., Beiser, Alexa S., Francks, Clyde, Saykin, Andrew J., Mather, Karen A., Romanczuk-Seiferth, Nina, Hartman, Catharina A., DeStefano, Anita L., Heslenfeld, Dirk J., Weiner, Michael W., Walter, Henrik, Hoekstra, Pieter J., Nyquist, Paul A., Franke, Barbara, Bennett, David A., Grabe, Hans J., Johnson, Andrew D., Chen, Christopher, van Duijn, Cornelia M., Lopez, Oscar L., Fornage, Myriam, Wardlaw, Joanna M., Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L., Villringer, Arno, Debette, Stephanie, Gudnason, Vilmundur, Medland, Sarah E., Shulman, Joshua M., Thompson, Paul M., Seshadri, Sudha, and Ikram, M. Arfan
Abstract: Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Published: 2019
Full Text: View/download PDF

11. Genetic architecture of subcortical brain structures in 38,851 individuals

Author: Satizabal, Claudia L, Adams, Hieab H H, Hibar, Derrek P, White, Charles C, Knol, Maria J, Stein, Jason L, Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V, Smith, Albert V, Bis, Joshua C, Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J, Yang, Jingyun, Yanek, Lisa R, Lee, Tom V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D, Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentería, Miguel E, Kim, Sungeun, Hoehn, David, Armstrong, Nicola J, Chen, Qiang, Holmes, Avram J, den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santiañez, Roberto, Kraemer, Bernd, Håberg, Asta K, Jones, Hannah J, Pike, G Bruce, Stein, Dan J, Stevens, Allison, Bralten, Janita, Vernooij, Meike W, Harris, Tamara B, Filippi, Irina, Witte, A Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H, Becker, James T, Doan, Nhat Trung, Hagenaars, Saskia P, Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M, Ames, David, Goldman, Aaron L, Lee, Phil H, Boomsma, Dorret I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M, Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M, Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E, Shin, Jean, Ipser, Jonathan C, Vinke, Louis N, Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K, Aribisala, Benjamin S, Schmidt, Helena, Strike, Lachlan T, Cheng, Ching-Yu, Risacher, Shannon L, Pütz, Benno, Fleischman, Debra A, Assareh, Amelia A, Mattay, Venkata S, Buckner, Randy L, Mecocci, Patrizia, Dale, Anders M, Cichon, Sven, Boks, Marco P, Matarin, Mar, Penninx, Brenda W J H, Calhoun, Vince D, Chakravarty, M Mallar, Marquand, Andre F, Macare, Christine, Kharabian Masouleh, Shahrzad, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome I, Schork, Andrew J, Liewald, David C M, de Zubicaray, Greig I, Wong, Tien Yin, Shen, Li, Sämann, Philipp G, Brodaty, Henry, Roffman, Joshua L, de Geus, Eco J C, Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R, Cavalleri, Gianpiero L, van der Wee, Nic J A, McIntosh, Andrew M, Gollub, Randy L, Bulayeva, Kazima B, Bernard, Manon, Richards, Jennifer S, Himali, Jayandra J, Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T, Valdés Hernández, Maria C, Hansell, Narelle K, van Erp, Theo G M, Wolf, Christiane, Kwok, John B J, Vellas, Bruno, Heinz, Andreas, Olde Loohuis, Loes M, Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R K, Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M, Bastin, Mark E, Montgomery, Grant W, Foroud, Tatiana M, Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D, van Donkelaar, Marjolein M J, Yang, Qiong, Hosten, Norbert, Green, Robert C, Thalamuthu, Anbupalam, Mohnke, Sebastian, Hulshoff Pol, Hilleke E, Lin, Honghuang, Jack, Clifford R, Schofield, Peter R, Mühleisen, Thomas W, Maillard, Pauline, Potkin, Steven G, Wen, Wei, Fletcher, Evan, Toga, Arthur W, Gruber, Oliver, Huentelman, Matthew, Davey Smith, George, Launer, Lenore J, Nyberg, Lars, Jönsson, Erik G, Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N, Uitterlinden, André G, Weinberger, Daniel R, Steen, Vidar M, Fedko, Iryna O, Groenewold, Nynke A, Niessen, Wiro J, Toro, Roberto, Tzourio, Christophe, Longstreth, William T, Ikram, M Kamran, Smoller, Jordan W, van Tol, Marie-Jose, Sussmann, Jessika E, Paus, Tomas, Lemaître, Hervé, Schroeter, Matthias L, Mazoyer, Bernard, Andreassen, Ole A, Holsboer, Florian, Depondt, Chantal, Veltman, Dick J, Turner, Jessica A, Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J, McMahon, Katie L, Müller-Myhsok, Bertram, Brouwer, Rachel M, Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H, Cheung, Joshua W, Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P, Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G, Kanai, Ryota, Westman, Eric, Kahn, René S, Sisodiya, Sanjay M, White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G, Völzke, Henry, Wright, Margaret J, van 't Ent, Dennis, Nöthen, Markus M, Ophoff, Roel A, Buitelaar, Jan K, Fernández, Guillén, Sachdev, Perminder S, Rietschel, Marcella, van Haren, Neeltje E M, Fisher, Simon E, Beiser, Alexa S, Francks, Clyde, Saykin, Andrew J, Mather, Karen A, Romanczuk-Seiferth, Nina, Hartman, Catharina A, DeStefano, Anita L, Heslenfeld, Dirk J, Weiner, Michael W, Walter, Henrik, Hoekstra, Pieter J, Nyquist, Paul A, Franke, Barbara, Bennett, David A, Grabe, Hans J, Johnson, Andrew D, Chen, Christopher, van Duijn, Cornelia M, Lopez, Oscar L, Fornage, Myriam, Wardlaw, Joanna M, Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L, Villringer, Arno, Debette, Stéphanie, Gudnason, Vilmundur, Medland, Sarah E, Shulman, Joshua M, Thompson, Paul M, Seshadri, Sudha, Ikram, M Arfan, Satizabal, Claudia L, Adams, Hieab H H, Hibar, Derrek P, White, Charles C, Knol, Maria J, Stein, Jason L, Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V, Smith, Albert V, Bis, Joshua C, Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J, Yang, Jingyun, Yanek, Lisa R, Lee, Tom V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D, Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentería, Miguel E, Kim, Sungeun, Hoehn, David, Armstrong, Nicola J, Chen, Qiang, Holmes, Avram J, den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santiañez, Roberto, Kraemer, Bernd, Håberg, Asta K, Jones, Hannah J, Pike, G Bruce, Stein, Dan J, Stevens, Allison, Bralten, Janita, Vernooij, Meike W, Harris, Tamara B, Filippi, Irina, Witte, A Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H, Becker, James T, Doan, Nhat Trung, Hagenaars, Saskia P, Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M, Ames, David, Goldman, Aaron L, Lee, Phil H, Boomsma, Dorret I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M, Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M, Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E, Shin, Jean, Ipser, Jonathan C, Vinke, Louis N, Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K, Aribisala, Benjamin S, Schmidt, Helena, Strike, Lachlan T, Cheng, Ching-Yu, Risacher, Shannon L, Pütz, Benno, Fleischman, Debra A, Assareh, Amelia A, Mattay, Venkata S, Buckner, Randy L, Mecocci, Patrizia, Dale, Anders M, Cichon, Sven, Boks, Marco P, Matarin, Mar, Penninx, Brenda W J H, Calhoun, Vince D, Chakravarty, M Mallar, Marquand, Andre F, Macare, Christine, Kharabian Masouleh, Shahrzad, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome I, Schork, Andrew J, Liewald, David C M, de Zubicaray, Greig I, Wong, Tien Yin, Shen, Li, Sämann, Philipp G, Brodaty, Henry, Roffman, Joshua L, de Geus, Eco J C, Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R, Cavalleri, Gianpiero L, van der Wee, Nic J A, McIntosh, Andrew M, Gollub, Randy L, Bulayeva, Kazima B, Bernard, Manon, Richards, Jennifer S, Himali, Jayandra J, Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T, Valdés Hernández, Maria C, Hansell, Narelle K, van Erp, Theo G M, Wolf, Christiane, Kwok, John B J, Vellas, Bruno, Heinz, Andreas, Olde Loohuis, Loes M, Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R K, Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M, Bastin, Mark E, Montgomery, Grant W, Foroud, Tatiana M, Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D, van Donkelaar, Marjolein M J, Yang, Qiong, Hosten, Norbert, Green, Robert C, Thalamuthu, Anbupalam, Mohnke, Sebastian, Hulshoff Pol, Hilleke E, Lin, Honghuang, Jack, Clifford R, Schofield, Peter R, Mühleisen, Thomas W, Maillard, Pauline, Potkin, Steven G, Wen, Wei, Fletcher, Evan, Toga, Arthur W, Gruber, Oliver, Huentelman, Matthew, Davey Smith, George, Launer, Lenore J, Nyberg, Lars, Jönsson, Erik G, Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N, Uitterlinden, André G, Weinberger, Daniel R, Steen, Vidar M, Fedko, Iryna O, Groenewold, Nynke A, Niessen, Wiro J, Toro, Roberto, Tzourio, Christophe, Longstreth, William T, Ikram, M Kamran, Smoller, Jordan W, van Tol, Marie-Jose, Sussmann, Jessika E, Paus, Tomas, Lemaître, Hervé, Schroeter, Matthias L, Mazoyer, Bernard, Andreassen, Ole A, Holsboer, Florian, Depondt, Chantal, Veltman, Dick J, Turner, Jessica A, Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J, McMahon, Katie L, Müller-Myhsok, Bertram, Brouwer, Rachel M, Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H, Cheung, Joshua W, Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P, Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G, Kanai, Ryota, Westman, Eric, Kahn, René S, Sisodiya, Sanjay M, White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G, Völzke, Henry, Wright, Margaret J, van 't Ent, Dennis, Nöthen, Markus M, Ophoff, Roel A, Buitelaar, Jan K, Fernández, Guillén, Sachdev, Perminder S, Rietschel, Marcella, van Haren, Neeltje E M, Fisher, Simon E, Beiser, Alexa S, Francks, Clyde, Saykin, Andrew J, Mather, Karen A, Romanczuk-Seiferth, Nina, Hartman, Catharina A, DeStefano, Anita L, Heslenfeld, Dirk J, Weiner, Michael W, Walter, Henrik, Hoekstra, Pieter J, Nyquist, Paul A, Franke, Barbara, Bennett, David A, Grabe, Hans J, Johnson, Andrew D, Chen, Christopher, van Duijn, Cornelia M, Lopez, Oscar L, Fornage, Myriam, Wardlaw, Joanna M, Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L, Villringer, Arno, Debette, Stéphanie, Gudnason, Vilmundur, Medland, Sarah E, Shulman, Joshua M, Thompson, Paul M, Seshadri, Sudha, and Ikram, M Arfan
Abstract: Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Published: 2019
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12. Multi-site meta-analysis of morphometry

Author: Jahanshad, Neda, Faskowitz, Joshua, Roshchupkin, Gennady, Hibar, Derrek P., Gutman, Boris A., Tustison, Nicholas J., Adams, Hieab H.H., Niessen, Wiro J., Vernooij, Meike W., Ikram, M. Arfan, Zwiers, Marcel P., Vasquez, Alejandro Arias, Franke, Barbara, Kroll, Jennifer L., Mwangi, Benson, Soares, Jair C., Ing, Alex, Desrivieres, Sylvane, Schumann, Gunter, Hansell, Narelle K., De Zubicaray, Greig I., McMahon, Katie L., Martin, Nicholas G., Wright, Margaret J., Thompson, Paul M., Jahanshad, Neda, Faskowitz, Joshua, Roshchupkin, Gennady, Hibar, Derrek P., Gutman, Boris A., Tustison, Nicholas J., Adams, Hieab H.H., Niessen, Wiro J., Vernooij, Meike W., Ikram, M. Arfan, Zwiers, Marcel P., Vasquez, Alejandro Arias, Franke, Barbara, Kroll, Jennifer L., Mwangi, Benson, Soares, Jair C., Ing, Alex, Desrivieres, Sylvane, Schumann, Gunter, Hansell, Narelle K., De Zubicaray, Greig I., McMahon, Katie L., Martin, Nicholas G., Wright, Margaret J., and Thompson, Paul M.
Abstract: Genome-wide association studies GWAS link full genome data to a handful of traits. However, in neuroimaging studies, there is an almost unlimited number of traits that can be extracted for full image-wide big data analyses. Large populations are needed to achieve the necessary power to detect statistically significant effects, emphasizing the need to pool data across multiple studies. Neuroimaging consortia, e.g., ENIGMA and CHARGE, are now analyzing MRI data from over 30,000 individuals. Distributed processing protocols extract harmonized features at each site, and pool together only the cohort statistics using meta analysis to avoid data sharing. To date, such MRI projects have focused on single measures such as hippocampal volume, yet voxelwise analyses e.g., tensor-based morphometry; TBM may help better localize statistical effects. This can lead to 1013 tests for GWAS and become underpowered. We developed an analytical framework for multi-site TBM by performing multi-channel registration to cohort-specific templates. Our results highlight the reliability of the method and the added power over alternative options while preserving single site specificity and opening the doors for well-powered image-wide genome-wide discoveries.
Published: 2019

13. Absolute and relative estimates of genetic and environmental variance in brain structure volumes

Author: Strike, Lachlan T., Hansell, Narelle K., Thompson, Paul M., de Zubicaray, Greig I., McMahon, Katie L., Zietsch, Brendan P., Wright, Margaret J., Strike, Lachlan T., Hansell, Narelle K., Thompson, Paul M., de Zubicaray, Greig I., McMahon, Katie L., Zietsch, Brendan P., and Wright, Margaret J.
Abstract: Comparing estimates of the amount of genetic and environmental variance for different brain structures may elucidate differences in the genetic architecture or developmental constraints of individual brain structures. However, most studies compare estimates of relative genetic (heritability) and environmental variance in brain structure, which do not reflect differences in absolute variance between brain regions. Here we used a population sample of young adult twins and singleton siblings of twins (n = 791; M = 23 years, Queensland Twin IMaging study) to estimate the absolute genetic and environmental variance, standardised by the phenotypic mean, in the size of cortical, subcortical, and ventricular brain structures. Mean-standardised genetic variance differed widely across structures [23.5-fold range 0.52% (hippocampus) to 12.28% (lateral ventricles)], but the range of estimates within cortical, subcortical, or ventricular structures was more moderate (two to fivefold range). There was no association between mean-standardised and relative measures of genetic variance (i.e., heritability) in brain structure volumes. We found similar results in an independent sample (n = 1075, M = 29 years, Human Connectome Project). These findings open important new lines of enquiry: namely, understanding the bases of these variance patterns, and their implications regarding the genetic architecture, evolution, and development of the human brain.
Published: 2019

14. Genetic architecture of subcortical brain structures in 38,851 individuals

Author: Satizabal, Claudia L., Adams, Hieab H.H., Hibar, Derrek P., White, Charles C., Knol, Maria J, Stein, Jason L, Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V, Smith, Albert V, Bis, Joshua C, Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J, Yang, Jingyun, Yanek, Lisa R, Lee, Tom V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D, Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentería, Miguel E, Kim, Sungeun, Hoehn, David, Armstrong, Nicola J, Chen, Qiang, Holmes, Avram J, den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santiañez, Roberto, Kraemer, Bernd, Håberg, Asta K, Jones, Hannah J, Pike, G Bruce, Stein, Dan J, Stevens, Allison, Bralten, Janita, Vernooij, Meike W, Harris, Tamara B, Filippi, Irina, Witte, A Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H, Becker, James T, Doan, Nhat Trung, Hagenaars, Saskia P, Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M, Ames, David, Goldman, Aaron L, Lee, Phil H, Boomsma, Dorret I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M, Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M, Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E, Shin, Jean, Ipser, Jonathan C, Vinke, Louis N, Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K, Aribisala, Benjamin S, Schmidt, Helena, Strike, Lachlan T, Cheng, Ching-Yu, Risacher, Shannon L, Pütz, Benno, Fleischman, Debra A, Assareh, Amelia A, Mattay, Venkata S, Buckner, Randy L, Mecocci, Patrizia, Dale, Anders M, Cichon, Sven, Boks, Marco P, Matarin, Mar, Penninx, Brenda W J H, Calhoun, Vince D, Chakravarty, M Mallar, Marquand, Andre F, Macare, Christine, Kharabian Masouleh, Shahrzad, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome I, Schork, Andrew J, Liewald, David C M, de Zubicaray, Greig I, Wong, Tien Yin, Shen, Li, Sämann, Philipp G, Brodaty, Henry, Roffman, Joshua L, de Geus, Eco J C, Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R, Cavalleri, Gianpiero L, van der Wee, Nic J A, McIntosh, Andrew M, Gollub, Randy L, Bulayeva, Kazima B, Bernard, Manon, Richards, Jennifer S, Himali, Jayandra J, Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T, Valdés Hernández, Maria C, Hansell, Narelle K, van Erp, Theo G M, Wolf, Christiane, Kwok, John B J, Vellas, Bruno, Heinz, Andreas, Olde Loohuis, Loes M, Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R K, Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M, Bastin, Mark E, Montgomery, Grant W, Foroud, Tatiana M, Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D, van Donkelaar, Marjolein M J, Yang, Qiong, Hosten, Norbert, Green, Robert C, Thalamuthu, Anbupalam, Mohnke, Sebastian, Hulshoff Pol, Hilleke E, Lin, Honghuang, Jack, Clifford R, Schofield, Peter R, Mühleisen, Thomas W, Maillard, Pauline, Potkin, Steven G, Wen, Wei, Fletcher, Evan, Toga, Arthur W, Gruber, Oliver, Huentelman, Matthew, Davey Smith, George, Launer, Lenore J, Nyberg, Lars, Jönsson, Erik G, Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N, Uitterlinden, André G, Weinberger, Daniel R, Steen, Vidar M, Fedko, Iryna O, Groenewold, Nynke A, Niessen, Wiro J, Toro, Roberto, Tzourio, Christophe, Longstreth, William T, Ikram, M Kamran, Smoller, Jordan W, van Tol, Marie-Jose, Sussmann, Jessika E, Paus, Tomas, Lemaître, Hervé, Schroeter, Matthias L, Mazoyer, Bernard, Andreassen, Ole A, Holsboer, Florian, Depondt, Chantal, Veltman, Dick J, Turner, Jessica A, Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J, McMahon, Katie L, Müller-Myhsok, Bertram, Brouwer, Rachel M, Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H, Cheung, Joshua W, Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P, Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G, Kanai, Ryota, Westman, Eric, Kahn, René S, Sisodiya, Sanjay M, White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G, Völzke, Henry, Wright, Margaret J, van 't Ent, Dennis, Nöthen, Markus M, Ophoff, Roel A, Buitelaar, Jan K, Fernández, Guillén, Sachdev, Perminder S, Rietschel, Marcella, van Haren, Neeltje E M, Fisher, Simon E, Beiser, Alexa S, Francks, Clyde, Saykin, Andrew J, Mather, Karen A, Romanczuk-Seiferth, Nina, Hartman, Catharina A, DeStefano, Anita L, Heslenfeld, Dirk J, Weiner, Michael W, Walter, Henrik, Hoekstra, Pieter J, Nyquist, Paul A, Franke, Barbara, Bennett, David A, Grabe, Hans J, Johnson, Andrew D, Chen, Christopher, van Duijn, Cornelia M, Lopez, Oscar L, Fornage, Myriam, Wardlaw, Joanna M, Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L, Villringer, Arno, Debette, Stéphanie, Gudnason, Vilmundur, Medland, Sarah E, Shulman, Joshua M, Thompson, Paul M, Seshadri, Sudha, Ikram, M Arfan, Satizabal, Claudia L., Adams, Hieab H.H., Hibar, Derrek P., White, Charles C., Knol, Maria J, Stein, Jason L, Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V, Smith, Albert V, Bis, Joshua C, Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J, Yang, Jingyun, Yanek, Lisa R, Lee, Tom V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D, Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentería, Miguel E, Kim, Sungeun, Hoehn, David, Armstrong, Nicola J, Chen, Qiang, Holmes, Avram J, den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santiañez, Roberto, Kraemer, Bernd, Håberg, Asta K, Jones, Hannah J, Pike, G Bruce, Stein, Dan J, Stevens, Allison, Bralten, Janita, Vernooij, Meike W, Harris, Tamara B, Filippi, Irina, Witte, A Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H, Becker, James T, Doan, Nhat Trung, Hagenaars, Saskia P, Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M, Ames, David, Goldman, Aaron L, Lee, Phil H, Boomsma, Dorret I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M, Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M, Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E, Shin, Jean, Ipser, Jonathan C, Vinke, Louis N, Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K, Aribisala, Benjamin S, Schmidt, Helena, Strike, Lachlan T, Cheng, Ching-Yu, Risacher, Shannon L, Pütz, Benno, Fleischman, Debra A, Assareh, Amelia A, Mattay, Venkata S, Buckner, Randy L, Mecocci, Patrizia, Dale, Anders M, Cichon, Sven, Boks, Marco P, Matarin, Mar, Penninx, Brenda W J H, Calhoun, Vince D, Chakravarty, M Mallar, Marquand, Andre F, Macare, Christine, Kharabian Masouleh, Shahrzad, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome I, Schork, Andrew J, Liewald, David C M, de Zubicaray, Greig I, Wong, Tien Yin, Shen, Li, Sämann, Philipp G, Brodaty, Henry, Roffman, Joshua L, de Geus, Eco J C, Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R, Cavalleri, Gianpiero L, van der Wee, Nic J A, McIntosh, Andrew M, Gollub, Randy L, Bulayeva, Kazima B, Bernard, Manon, Richards, Jennifer S, Himali, Jayandra J, Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T, Valdés Hernández, Maria C, Hansell, Narelle K, van Erp, Theo G M, Wolf, Christiane, Kwok, John B J, Vellas, Bruno, Heinz, Andreas, Olde Loohuis, Loes M, Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R K, Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M, Bastin, Mark E, Montgomery, Grant W, Foroud, Tatiana M, Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D, van Donkelaar, Marjolein M J, Yang, Qiong, Hosten, Norbert, Green, Robert C, Thalamuthu, Anbupalam, Mohnke, Sebastian, Hulshoff Pol, Hilleke E, Lin, Honghuang, Jack, Clifford R, Schofield, Peter R, Mühleisen, Thomas W, Maillard, Pauline, Potkin, Steven G, Wen, Wei, Fletcher, Evan, Toga, Arthur W, Gruber, Oliver, Huentelman, Matthew, Davey Smith, George, Launer, Lenore J, Nyberg, Lars, Jönsson, Erik G, Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N, Uitterlinden, André G, Weinberger, Daniel R, Steen, Vidar M, Fedko, Iryna O, Groenewold, Nynke A, Niessen, Wiro J, Toro, Roberto, Tzourio, Christophe, Longstreth, William T, Ikram, M Kamran, Smoller, Jordan W, van Tol, Marie-Jose, Sussmann, Jessika E, Paus, Tomas, Lemaître, Hervé, Schroeter, Matthias L, Mazoyer, Bernard, Andreassen, Ole A, Holsboer, Florian, Depondt, Chantal, Veltman, Dick J, Turner, Jessica A, Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J, McMahon, Katie L, Müller-Myhsok, Bertram, Brouwer, Rachel M, Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H, Cheung, Joshua W, Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P, Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G, Kanai, Ryota, Westman, Eric, Kahn, René S, Sisodiya, Sanjay M, White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G, Völzke, Henry, Wright, Margaret J, van 't Ent, Dennis, Nöthen, Markus M, Ophoff, Roel A, Buitelaar, Jan K, Fernández, Guillén, Sachdev, Perminder S, Rietschel, Marcella, van Haren, Neeltje E M, Fisher, Simon E, Beiser, Alexa S, Francks, Clyde, Saykin, Andrew J, Mather, Karen A, Romanczuk-Seiferth, Nina, Hartman, Catharina A, DeStefano, Anita L, Heslenfeld, Dirk J, Weiner, Michael W, Walter, Henrik, Hoekstra, Pieter J, Nyquist, Paul A, Franke, Barbara, Bennett, David A, Grabe, Hans J, Johnson, Andrew D, Chen, Christopher, van Duijn, Cornelia M, Lopez, Oscar L, Fornage, Myriam, Wardlaw, Joanna M, Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L, Villringer, Arno, Debette, Stéphanie, Gudnason, Vilmundur, Medland, Sarah E, Shulman, Joshua M, Thompson, Paul M, Seshadri, Sudha, and Ikram, M Arfan
Abstract: Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Published: 2019

15. Genetic architecture of subcortical brain structures in 38,851 individuals

Author: Satizabal, Claudia L, Adams, Hieab H H, Hibar, Derrek P, White, Charles C, Knol, Maria J, Stein, Jason L, Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V, Smith, Albert V, Bis, Joshua C, Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J, Yang, Jingyun, Yanek, Lisa R, Lee, Tom V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D, Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentería, Miguel E, Kim, Sungeun, Hoehn, David, Armstrong, Nicola J, Chen, Qiang, Holmes, Avram J, den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santiañez, Roberto, Kraemer, Bernd, Håberg, Asta K, Jones, Hannah J, Pike, G Bruce, Stein, Dan J, Stevens, Allison, Bralten, Janita, Vernooij, Meike W, Harris, Tamara B, Filippi, Irina, Witte, A Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H, Becker, James T, Doan, Nhat Trung, Hagenaars, Saskia P, Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M, Ames, David, Goldman, Aaron L, Lee, Phil H, Boomsma, Dorret I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M, Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M, Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E, Shin, Jean, Ipser, Jonathan C, Vinke, Louis N, Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K, Aribisala, Benjamin S, Schmidt, Helena, Strike, Lachlan T, Cheng, Ching-Yu, Risacher, Shannon L, Pütz, Benno, Fleischman, Debra A, Assareh, Amelia A, Mattay, Venkata S, Buckner, Randy L, Mecocci, Patrizia, Dale, Anders M, Cichon, Sven, Boks, Marco P, Matarin, Mar, Penninx, Brenda W J H, Calhoun, Vince D, Chakravarty, M Mallar, Marquand, Andre F, Macare, Christine, Kharabian Masouleh, Shahrzad, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome I, Schork, Andrew J, Liewald, David C M, de Zubicaray, Greig I, Wong, Tien Yin, Shen, Li, Sämann, Philipp G, Brodaty, Henry, Roffman, Joshua L, de Geus, Eco J C, Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R, Cavalleri, Gianpiero L, van der Wee, Nic J A, McIntosh, Andrew M, Gollub, Randy L, Bulayeva, Kazima B, Bernard, Manon, Richards, Jennifer S, Himali, Jayandra J, Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T, Valdés Hernández, Maria C, Hansell, Narelle K, van Erp, Theo G M, Wolf, Christiane, Kwok, John B J, Vellas, Bruno, Heinz, Andreas, Olde Loohuis, Loes M, Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R K, Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M, Bastin, Mark E, Montgomery, Grant W, Foroud, Tatiana M, Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D, van Donkelaar, Marjolein M J, Yang, Qiong, Hosten, Norbert, Green, Robert C, Thalamuthu, Anbupalam, Mohnke, Sebastian, Hulshoff Pol, Hilleke E, Lin, Honghuang, Jack, Clifford R, Schofield, Peter R, Mühleisen, Thomas W, Maillard, Pauline, Potkin, Steven G, Wen, Wei, Fletcher, Evan, Toga, Arthur W, Gruber, Oliver, Huentelman, Matthew, Davey Smith, George, Launer, Lenore J, Nyberg, Lars, Jönsson, Erik G, Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N, Uitterlinden, André G, Weinberger, Daniel R, Steen, Vidar M, Fedko, Iryna O, Groenewold, Nynke A, Niessen, Wiro J, Toro, Roberto, Tzourio, Christophe, Longstreth, William T, Ikram, M Kamran, Smoller, Jordan W, van Tol, Marie-Jose, Sussmann, Jessika E, Paus, Tomas, Lemaître, Hervé, Schroeter, Matthias L, Mazoyer, Bernard, Andreassen, Ole A, Holsboer, Florian, Depondt, Chantal, Veltman, Dick J, Turner, Jessica A, Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J, McMahon, Katie L, Müller-Myhsok, Bertram, Brouwer, Rachel M, Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H, Cheung, Joshua W, Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P, Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G, Kanai, Ryota, Westman, Eric, Kahn, René S, Sisodiya, Sanjay M, White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G, Völzke, Henry, Wright, Margaret J, van 't Ent, Dennis, Nöthen, Markus M, Ophoff, Roel A, Buitelaar, Jan K, Fernández, Guillén, Sachdev, Perminder S, Rietschel, Marcella, van Haren, Neeltje E M, Fisher, Simon E, Beiser, Alexa S, Francks, Clyde, Saykin, Andrew J, Mather, Karen A, Romanczuk-Seiferth, Nina, Hartman, Catharina A, DeStefano, Anita L, Heslenfeld, Dirk J, Weiner, Michael W, Walter, Henrik, Hoekstra, Pieter J, Nyquist, Paul A, Franke, Barbara, Bennett, David A, Grabe, Hans J, Johnson, Andrew D, Chen, Christopher, van Duijn, Cornelia M, Lopez, Oscar L, Fornage, Myriam, Wardlaw, Joanna M, Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L, Villringer, Arno, Debette, Stéphanie, Gudnason, Vilmundur, Medland, Sarah E, Shulman, Joshua M, Thompson, Paul M, Seshadri, Sudha, Ikram, M Arfan, Satizabal, Claudia L, Adams, Hieab H H, Hibar, Derrek P, White, Charles C, Knol, Maria J, Stein, Jason L, Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V, Smith, Albert V, Bis, Joshua C, Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J, Yang, Jingyun, Yanek, Lisa R, Lee, Tom V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D, Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentería, Miguel E, Kim, Sungeun, Hoehn, David, Armstrong, Nicola J, Chen, Qiang, Holmes, Avram J, den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santiañez, Roberto, Kraemer, Bernd, Håberg, Asta K, Jones, Hannah J, Pike, G Bruce, Stein, Dan J, Stevens, Allison, Bralten, Janita, Vernooij, Meike W, Harris, Tamara B, Filippi, Irina, Witte, A Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H, Becker, James T, Doan, Nhat Trung, Hagenaars, Saskia P, Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M, Ames, David, Goldman, Aaron L, Lee, Phil H, Boomsma, Dorret I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M, Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M, Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E, Shin, Jean, Ipser, Jonathan C, Vinke, Louis N, Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K, Aribisala, Benjamin S, Schmidt, Helena, Strike, Lachlan T, Cheng, Ching-Yu, Risacher, Shannon L, Pütz, Benno, Fleischman, Debra A, Assareh, Amelia A, Mattay, Venkata S, Buckner, Randy L, Mecocci, Patrizia, Dale, Anders M, Cichon, Sven, Boks, Marco P, Matarin, Mar, Penninx, Brenda W J H, Calhoun, Vince D, Chakravarty, M Mallar, Marquand, Andre F, Macare, Christine, Kharabian Masouleh, Shahrzad, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome I, Schork, Andrew J, Liewald, David C M, de Zubicaray, Greig I, Wong, Tien Yin, Shen, Li, Sämann, Philipp G, Brodaty, Henry, Roffman, Joshua L, de Geus, Eco J C, Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R, Cavalleri, Gianpiero L, van der Wee, Nic J A, McIntosh, Andrew M, Gollub, Randy L, Bulayeva, Kazima B, Bernard, Manon, Richards, Jennifer S, Himali, Jayandra J, Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T, Valdés Hernández, Maria C, Hansell, Narelle K, van Erp, Theo G M, Wolf, Christiane, Kwok, John B J, Vellas, Bruno, Heinz, Andreas, Olde Loohuis, Loes M, Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R K, Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M, Bastin, Mark E, Montgomery, Grant W, Foroud, Tatiana M, Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D, van Donkelaar, Marjolein M J, Yang, Qiong, Hosten, Norbert, Green, Robert C, Thalamuthu, Anbupalam, Mohnke, Sebastian, Hulshoff Pol, Hilleke E, Lin, Honghuang, Jack, Clifford R, Schofield, Peter R, Mühleisen, Thomas W, Maillard, Pauline, Potkin, Steven G, Wen, Wei, Fletcher, Evan, Toga, Arthur W, Gruber, Oliver, Huentelman, Matthew, Davey Smith, George, Launer, Lenore J, Nyberg, Lars, Jönsson, Erik G, Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N, Uitterlinden, André G, Weinberger, Daniel R, Steen, Vidar M, Fedko, Iryna O, Groenewold, Nynke A, Niessen, Wiro J, Toro, Roberto, Tzourio, Christophe, Longstreth, William T, Ikram, M Kamran, Smoller, Jordan W, van Tol, Marie-Jose, Sussmann, Jessika E, Paus, Tomas, Lemaître, Hervé, Schroeter, Matthias L, Mazoyer, Bernard, Andreassen, Ole A, Holsboer, Florian, Depondt, Chantal, Veltman, Dick J, Turner, Jessica A, Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J, McMahon, Katie L, Müller-Myhsok, Bertram, Brouwer, Rachel M, Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H, Cheung, Joshua W, Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P, Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G, Kanai, Ryota, Westman, Eric, Kahn, René S, Sisodiya, Sanjay M, White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G, Völzke, Henry, Wright, Margaret J, van 't Ent, Dennis, Nöthen, Markus M, Ophoff, Roel A, Buitelaar, Jan K, Fernández, Guillén, Sachdev, Perminder S, Rietschel, Marcella, van Haren, Neeltje E M, Fisher, Simon E, Beiser, Alexa S, Francks, Clyde, Saykin, Andrew J, Mather, Karen A, Romanczuk-Seiferth, Nina, Hartman, Catharina A, DeStefano, Anita L, Heslenfeld, Dirk J, Weiner, Michael W, Walter, Henrik, Hoekstra, Pieter J, Nyquist, Paul A, Franke, Barbara, Bennett, David A, Grabe, Hans J, Johnson, Andrew D, Chen, Christopher, van Duijn, Cornelia M, Lopez, Oscar L, Fornage, Myriam, Wardlaw, Joanna M, Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L, Villringer, Arno, Debette, Stéphanie, Gudnason, Vilmundur, Medland, Sarah E, Shulman, Joshua M, Thompson, Paul M, Seshadri, Sudha, and Ikram, M Arfan
Abstract: Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Published: 2019
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16. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, Deary, Ian J., Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, and Deary, Ian J.
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 x 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function., Errata: Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., … Deary, I. J. (2019). Author correction to Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. [Nature Communications (2018), 9, Article number 2098]. Nature Communications, 10, Article number: 2068. DOI: 10.1038/s41467-019-10160-w
Published: 2018
Full Text: View/download PDF

17. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, Deary, Ian J., Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, and Deary, Ian J.
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 x 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function., Errata: Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., … Deary, I. J. (2019). Author correction to Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. [Nature Communications (2018), 9, Article number 2098]. Nature Communications, 10, Article number: 2068. DOI: 10.1038/s41467-019-10160-w
Published: 2018
Full Text: View/download PDF

18. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, Deary, Ian J., Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, and Deary, Ian J.
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 x 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function., Errata: Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., … Deary, I. J. (2019). Author correction to Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. [Nature Communications (2018), 9, Article number 2098]. Nature Communications, 10, Article number: 2068. DOI: 10.1038/s41467-019-10160-w
Published: 2018
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19. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

Author: Savage, Jeanne E, Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan RI, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, Christiansen, Lene, Savage, Jeanne E, Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan RI, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, and Christiansen, Lene
Abstract: Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Published: 2018

20. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Göran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Bressler, Jan, Lencz, Todd, Deary, Ian J., Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Göran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Bressler, Jan, Lencz, Todd, and Deary, Ian J.
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 x 10(-8)) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
Published: 2018
Full Text: View/download PDF

21. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Davies, Gail, Lam, Max, Harris, Sarah E, Trampush, Joey W, Luciano, Michelle, Hill, W David, Hagenaars, Saskia P, Ritchie, Stuart J, Marioni, Riccardo E, Fawns-Ritchie, Chloe, Liewald, David CM, Okely, Judith A, Ahola-Olli, Ari V, Barnes, Catriona LK, Bertram, Lars, Bis, Joshua C, Burdick, Katherine E, Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E, Hayward, Caroline, Hofer, Edith, Ikram, M Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A, Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A, Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A, Smith, Albert V, Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J, Ware, Erin B, Windham, B Gwen, Wright, Margaret J, Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A, Armstrong, Nicola J, Assareh, Amelia A, Attia, John R, Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A, Böhmer, Anne C, Boyle, Patricia A, Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D, Cirulli, Elizabeth T, Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R, Dale, Anders M, Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G, Evangelou, Evangelos, Faul, Jessica D, Ford, Ian, Freimer, Nelson A, Gao, He, Giegling, Ina, Gillespie, Nathan A, Gordon, Scott D, Gottesman, Rebecca F, Griswold, Michael E, Gudnason, Vilmundur, Harris, Tamara B, Hartmann, Annette M, Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G, Joshi, Peter K, Kähönen, Mika, Kardia, Sharon LR, Karlsson, Ida, Kleineidam, Luca, Knopman, David S, Kochan, Nicole A, Konte, Bettina, Kwok, John B, Le Hellard, Stephanie, Lee, Teresa, Lehtimäki, Terho, Li, Shu-Chen, Lill, Christina M, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T, Lopez, Oscar L, Loukola, Anu, Luck, Tobias, Lundervold, Astri J, Lundquist, Anders, Lyytikäinen, Leo-Pekka, Martin, Nicholas G, Montgomery, Grant W, Murray, Alison D, Need, Anna C, Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A, Psaty, Bruce M, Reppermund, Simone, Riedel-Heller, Steffi G, Rose, Richard J, Rotter, Jerome I, Roussos, Panos, Rovio, Suvi P, Saba, Yasaman, Sabb, Fred W, Sachdev, Perminder S, Satizabal, Claudia L, Schmid, Matthias, Scott, Rodney J, Scult, Matthew A, Simino, Jeannette, Slagboom, P Eline, Smyrnis, Nikolaos, Soumaré, Aïcha, Stefanis, Nikos C, Stott, David J, Straub, Richard E, Sundet, Kjetil, Taylor, Adele M, Taylor, Kent D, Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André, Vitart, Veronique, Voineskos, Aristotle N, Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab HH, Arking, Dan E, Bilder, Robert M, Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L, Debette, Stéphanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L, Gill, Michael, Glahn, David C, Hägg, Sara, Hansell, Narelle K, Hariri, Ahmad R, Ikram, M Kamran, Jukema, J Wouter, Vuoksimaa, Eero, Keller, Matthew C, Kremen, William S, Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L, Pendleton, Neil, Porteous, David J, Räikkönen, Katri, Raitakari, Olli T, Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Dan Rujescu, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W, Schofield, Peter R, Starr, John M, Steen, Vidar M, Trollor, Julian N, Turner, Steven T, Van Duijn, Cornelia M, Villringer, Arno, Weinberger, Daniel R, Weir, David R, Wilson, James F, Malhotra, Anil, McIntosh, Andrew M, Gale, Catharine R, Seshadri, Sudha, Mosley, Thomas H, Bressler, Jan, Lencz, Todd, Deary, Ian J, Davies, Gail, Lam, Max, Harris, Sarah E, Trampush, Joey W, Luciano, Michelle, Hill, W David, Hagenaars, Saskia P, Ritchie, Stuart J, Marioni, Riccardo E, Fawns-Ritchie, Chloe, Liewald, David CM, Okely, Judith A, Ahola-Olli, Ari V, Barnes, Catriona LK, Bertram, Lars, Bis, Joshua C, Burdick, Katherine E, Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E, Hayward, Caroline, Hofer, Edith, Ikram, M Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A, Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A, Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A, Smith, Albert V, Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J, Ware, Erin B, Windham, B Gwen, Wright, Margaret J, Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A, Armstrong, Nicola J, Assareh, Amelia A, Attia, John R, Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A, Böhmer, Anne C, Boyle, Patricia A, Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D, Cirulli, Elizabeth T, Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R, Dale, Anders M, Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G, Evangelou, Evangelos, Faul, Jessica D, Ford, Ian, Freimer, Nelson A, Gao, He, Giegling, Ina, Gillespie, Nathan A, Gordon, Scott D, Gottesman, Rebecca F, Griswold, Michael E, Gudnason, Vilmundur, Harris, Tamara B, Hartmann, Annette M, Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G, Joshi, Peter K, Kähönen, Mika, Kardia, Sharon LR, Karlsson, Ida, Kleineidam, Luca, Knopman, David S, Kochan, Nicole A, Konte, Bettina, Kwok, John B, Le Hellard, Stephanie, Lee, Teresa, Lehtimäki, Terho, Li, Shu-Chen, Lill, Christina M, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T, Lopez, Oscar L, Loukola, Anu, Luck, Tobias, Lundervold, Astri J, Lundquist, Anders, Lyytikäinen, Leo-Pekka, Martin, Nicholas G, Montgomery, Grant W, Murray, Alison D, Need, Anna C, Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A, Psaty, Bruce M, Reppermund, Simone, Riedel-Heller, Steffi G, Rose, Richard J, Rotter, Jerome I, Roussos, Panos, Rovio, Suvi P, Saba, Yasaman, Sabb, Fred W, Sachdev, Perminder S, Satizabal, Claudia L, Schmid, Matthias, Scott, Rodney J, Scult, Matthew A, Simino, Jeannette, Slagboom, P Eline, Smyrnis, Nikolaos, Soumaré, Aïcha, Stefanis, Nikos C, Stott, David J, Straub, Richard E, Sundet, Kjetil, Taylor, Adele M, Taylor, Kent D, Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André, Vitart, Veronique, Voineskos, Aristotle N, Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab HH, Arking, Dan E, Bilder, Robert M, Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L, Debette, Stéphanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L, Gill, Michael, Glahn, David C, Hägg, Sara, Hansell, Narelle K, Hariri, Ahmad R, Ikram, M Kamran, Jukema, J Wouter, Vuoksimaa, Eero, Keller, Matthew C, Kremen, William S, Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L, Pendleton, Neil, Porteous, David J, Räikkönen, Katri, Raitakari, Olli T, Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Dan Rujescu, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W, Schofield, Peter R, Starr, John M, Steen, Vidar M, Trollor, Julian N, Turner, Steven T, Van Duijn, Cornelia M, Villringer, Arno, Weinberger, Daniel R, Weir, David R, Wilson, James F, Malhotra, Anil, McIntosh, Andrew M, Gale, Catharine R, Seshadri, Sudha, Mosley, Thomas H, Bressler, Jan, Lencz, Todd, and Deary, Ian J
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
Published: 2018

22. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Author: Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan RI, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, Christiansen, Lene, Debrabant, Birgit, Dick, Danielle M, Heinz, Andreas, Hjerling-Leffler, Jens, Ikram, M Arfan, Kendler, Kenneth S, Martin, Nicholas G, Medland, Sarah E, Pedersen, Nancy L, Plomin, Robert, Polderman, Tinca JC, Ripke, Stephan, van der Sluis, Sophie, Sullivan, Patrick F, Vrieze, Scott I, Wright, Margaret J, Posthuma, Danielle, Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan RI, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, Christiansen, Lene, Debrabant, Birgit, Dick, Danielle M, Heinz, Andreas, Hjerling-Leffler, Jens, Ikram, M Arfan, Kendler, Kenneth S, Martin, Nicholas G, Medland, Sarah E, Pedersen, Nancy L, Plomin, Robert, Polderman, Tinca JC, Ripke, Stephan, van der Sluis, Sophie, Sullivan, Patrick F, Vrieze, Scott I, Wright, Margaret J, and Posthuma, Danielle
Abstract: Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3,4,5,6,7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer’s disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Published: 2018

23. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, Deary, Ian J., Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, and Deary, Ian J.
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 x 10(-8)) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
Published: 2018

24. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Author: Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan R I, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, Christiansen, Lene, Debrabant, Birgit, Dick, Danielle M, Heinz, Andreas, Hjerling-Leffler, Jens, Ikram, M Arfan, Kendler, Kenneth S, Martin, Nicholas G, Medland, Sarah E, Pedersen, Nancy L, Plomin, Robert, Polderman, Tinca J C, Ripke, Stephan, van der Sluis, Sophie, Sullivan, Patrick F, Vrieze, Scott I, Wright, Margaret J, Posthuma, Danielle, Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan R I, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, Christiansen, Lene, Debrabant, Birgit, Dick, Danielle M, Heinz, Andreas, Hjerling-Leffler, Jens, Ikram, M Arfan, Kendler, Kenneth S, Martin, Nicholas G, Medland, Sarah E, Pedersen, Nancy L, Plomin, Robert, Polderman, Tinca J C, Ripke, Stephan, van der Sluis, Sophie, Sullivan, Patrick F, Vrieze, Scott I, Wright, Margaret J, and Posthuma, Danielle
Abstract: Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Published: 2018
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25. Sex differences in cerebral blood flow in young adolescents

Author: van Eijk, Liza, Strike, Lachlan T., Hansell, Narelle K., Chuang, Kai-Hsiang, McMahon, Katie L., Zietsch, Brendan P., Wright, Margaret J., van Eijk, Liza, Strike, Lachlan T., Hansell, Narelle K., Chuang, Kai-Hsiang, McMahon, Katie L., Zietsch, Brendan P., and Wright, Margaret J.
Abstract: Research questions - Sex difference in cerebral blood flow (CBF) in young adolescents? - Is this sex difference in CBF influenced by puberty? Method - 130 young adolescents - the longitudinal Queensland Twin Adolescent Brain project, after excluding due to motion in ASL scans (18) or abnormality(10) - Puberty was classified into two groups: pre to early puberty (Tanner stage 1 - 2) (n=54), and mid to post puberty (Tanner stage 3 - 5) (n=51) - Siemens Prisma 3T scanner (Centre of Advanced Imaging): pCASL , 3x M0, FLAIR and 3D T1 images - Processing in Freesurfer , MATLAB, SPM, ASLtbx , and DARTEL - Voxel - wise and ROI analyses
Published: 2018

26. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

Author: Savage, Jeanne E, Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan RI, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, Christiansen, Lene, Savage, Jeanne E, Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan RI, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, and Christiansen, Lene
Abstract: Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Published: 2018

27. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Author: Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan RI, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, Christiansen, Lene, Debrabant, Birgit, Dick, Danielle M, Heinz, Andreas, Hjerling-Leffler, Jens, Ikram, M Arfan, Kendler, Kenneth S, Martin, Nicholas G, Medland, Sarah E, Pedersen, Nancy L, Plomin, Robert, Polderman, Tinca JC, Ripke, Stephan, van der Sluis, Sophie, Sullivan, Patrick F, Vrieze, Scott I, Wright, Margaret J, Posthuma, Danielle, Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan RI, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, Christiansen, Lene, Debrabant, Birgit, Dick, Danielle M, Heinz, Andreas, Hjerling-Leffler, Jens, Ikram, M Arfan, Kendler, Kenneth S, Martin, Nicholas G, Medland, Sarah E, Pedersen, Nancy L, Plomin, Robert, Polderman, Tinca JC, Ripke, Stephan, van der Sluis, Sophie, Sullivan, Patrick F, Vrieze, Scott I, Wright, Margaret J, and Posthuma, Danielle
Abstract: Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3,4,5,6,7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer’s disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Published: 2018

28. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Davies, Gail, Lam, Max, Harris, Sarah E, Trampush, Joey W, Luciano, Michelle, Hill, W David, Hagenaars, Saskia P, Ritchie, Stuart J, Marioni, Riccardo E, Fawns-Ritchie, Chloe, Liewald, David CM, Okely, Judith A, Ahola-Olli, Ari V, Barnes, Catriona LK, Bertram, Lars, Bis, Joshua C, Burdick, Katherine E, Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E, Hayward, Caroline, Hofer, Edith, Ikram, M Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A, Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A, Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A, Smith, Albert V, Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J, Ware, Erin B, Windham, B Gwen, Wright, Margaret J, Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A, Armstrong, Nicola J, Assareh, Amelia A, Attia, John R, Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A, Böhmer, Anne C, Boyle, Patricia A, Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D, Cirulli, Elizabeth T, Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R, Dale, Anders M, Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G, Evangelou, Evangelos, Faul, Jessica D, Ford, Ian, Freimer, Nelson A, Gao, He, Giegling, Ina, Gillespie, Nathan A, Gordon, Scott D, Gottesman, Rebecca F, Griswold, Michael E, Gudnason, Vilmundur, Harris, Tamara B, Hartmann, Annette M, Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G, Joshi, Peter K, Kähönen, Mika, Kardia, Sharon LR, Karlsson, Ida, Kleineidam, Luca, Knopman, David S, Kochan, Nicole A, Konte, Bettina, Kwok, John B, Le Hellard, Stephanie, Lee, Teresa, Lehtimäki, Terho, Li, Shu-Chen, Lill, Christina M, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T, Lopez, Oscar L, Loukola, Anu, Luck, Tobias, Lundervold, Astri J, Lundquist, Anders, Lyytikäinen, Leo-Pekka, Martin, Nicholas G, Montgomery, Grant W, Murray, Alison D, Need, Anna C, Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A, Psaty, Bruce M, Reppermund, Simone, Riedel-Heller, Steffi G, Rose, Richard J, Rotter, Jerome I, Roussos, Panos, Rovio, Suvi P, Saba, Yasaman, Sabb, Fred W, Sachdev, Perminder S, Satizabal, Claudia L, Schmid, Matthias, Scott, Rodney J, Scult, Matthew A, Simino, Jeannette, Slagboom, P Eline, Smyrnis, Nikolaos, Soumaré, Aïcha, Stefanis, Nikos C, Stott, David J, Straub, Richard E, Sundet, Kjetil, Taylor, Adele M, Taylor, Kent D, Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André, Vitart, Veronique, Voineskos, Aristotle N, Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab HH, Arking, Dan E, Bilder, Robert M, Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L, Debette, Stéphanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L, Gill, Michael, Glahn, David C, Hägg, Sara, Hansell, Narelle K, Hariri, Ahmad R, Ikram, M Kamran, Jukema, J Wouter, Vuoksimaa, Eero, Keller, Matthew C, Kremen, William S, Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L, Pendleton, Neil, Porteous, David J, Räikkönen, Katri, Raitakari, Olli T, Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Dan Rujescu, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W, Schofield, Peter R, Starr, John M, Steen, Vidar M, Trollor, Julian N, Turner, Steven T, Van Duijn, Cornelia M, Villringer, Arno, Weinberger, Daniel R, Weir, David R, Wilson, James F, Malhotra, Anil, McIntosh, Andrew M, Gale, Catharine R, Seshadri, Sudha, Mosley, Thomas H, Bressler, Jan, Lencz, Todd, Deary, Ian J, Davies, Gail, Lam, Max, Harris, Sarah E, Trampush, Joey W, Luciano, Michelle, Hill, W David, Hagenaars, Saskia P, Ritchie, Stuart J, Marioni, Riccardo E, Fawns-Ritchie, Chloe, Liewald, David CM, Okely, Judith A, Ahola-Olli, Ari V, Barnes, Catriona LK, Bertram, Lars, Bis, Joshua C, Burdick, Katherine E, Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E, Hayward, Caroline, Hofer, Edith, Ikram, M Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A, Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A, Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A, Smith, Albert V, Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J, Ware, Erin B, Windham, B Gwen, Wright, Margaret J, Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A, Armstrong, Nicola J, Assareh, Amelia A, Attia, John R, Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A, Böhmer, Anne C, Boyle, Patricia A, Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D, Cirulli, Elizabeth T, Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R, Dale, Anders M, Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G, Evangelou, Evangelos, Faul, Jessica D, Ford, Ian, Freimer, Nelson A, Gao, He, Giegling, Ina, Gillespie, Nathan A, Gordon, Scott D, Gottesman, Rebecca F, Griswold, Michael E, Gudnason, Vilmundur, Harris, Tamara B, Hartmann, Annette M, Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G, Joshi, Peter K, Kähönen, Mika, Kardia, Sharon LR, Karlsson, Ida, Kleineidam, Luca, Knopman, David S, Kochan, Nicole A, Konte, Bettina, Kwok, John B, Le Hellard, Stephanie, Lee, Teresa, Lehtimäki, Terho, Li, Shu-Chen, Lill, Christina M, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T, Lopez, Oscar L, Loukola, Anu, Luck, Tobias, Lundervold, Astri J, Lundquist, Anders, Lyytikäinen, Leo-Pekka, Martin, Nicholas G, Montgomery, Grant W, Murray, Alison D, Need, Anna C, Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A, Psaty, Bruce M, Reppermund, Simone, Riedel-Heller, Steffi G, Rose, Richard J, Rotter, Jerome I, Roussos, Panos, Rovio, Suvi P, Saba, Yasaman, Sabb, Fred W, Sachdev, Perminder S, Satizabal, Claudia L, Schmid, Matthias, Scott, Rodney J, Scult, Matthew A, Simino, Jeannette, Slagboom, P Eline, Smyrnis, Nikolaos, Soumaré, Aïcha, Stefanis, Nikos C, Stott, David J, Straub, Richard E, Sundet, Kjetil, Taylor, Adele M, Taylor, Kent D, Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André, Vitart, Veronique, Voineskos, Aristotle N, Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab HH, Arking, Dan E, Bilder, Robert M, Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L, Debette, Stéphanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L, Gill, Michael, Glahn, David C, Hägg, Sara, Hansell, Narelle K, Hariri, Ahmad R, Ikram, M Kamran, Jukema, J Wouter, Vuoksimaa, Eero, Keller, Matthew C, Kremen, William S, Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L, Pendleton, Neil, Porteous, David J, Räikkönen, Katri, Raitakari, Olli T, Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Dan Rujescu, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W, Schofield, Peter R, Starr, John M, Steen, Vidar M, Trollor, Julian N, Turner, Steven T, Van Duijn, Cornelia M, Villringer, Arno, Weinberger, Daniel R, Weir, David R, Wilson, James F, Malhotra, Anil, McIntosh, Andrew M, Gale, Catharine R, Seshadri, Sudha, Mosley, Thomas H, Bressler, Jan, Lencz, Todd, and Deary, Ian J
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
Published: 2018

29. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, Deary, Ian J., Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, and Deary, Ian J.
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 x 10(-8)) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
Published: 2018

30. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Author: Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan R I, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, Christiansen, Lene, Debrabant, Birgit, Dick, Danielle M, Heinz, Andreas, Hjerling-Leffler, Jens, Ikram, M Arfan, Kendler, Kenneth S, Martin, Nicholas G, Medland, Sarah E, Pedersen, Nancy L, Plomin, Robert, Polderman, Tinca J C, Ripke, Stephan, van der Sluis, Sophie, Sullivan, Patrick F, Vrieze, Scott I, Wright, Margaret J, Posthuma, Danielle, Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan R I, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, Christiansen, Lene, Debrabant, Birgit, Dick, Danielle M, Heinz, Andreas, Hjerling-Leffler, Jens, Ikram, M Arfan, Kendler, Kenneth S, Martin, Nicholas G, Medland, Sarah E, Pedersen, Nancy L, Plomin, Robert, Polderman, Tinca J C, Ripke, Stephan, van der Sluis, Sophie, Sullivan, Patrick F, Vrieze, Scott I, Wright, Margaret J, and Posthuma, Danielle
Abstract: Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Published: 2018
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31. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, Deary, Ian J., Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, and Deary, Ian J.
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 x 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function., Errata: Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., … Deary, I. J. (2019). Author correction to Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. [Nature Communications (2018), 9, Article number 2098]. Nature Communications, 10, Article number: 2068. DOI: 10.1038/s41467-019-10160-w
Published: 2018
Full Text: View/download PDF

32. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, Deary, Ian J., Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Boehmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kahonen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimaki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T., Jr., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikainen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumare, Aicha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stephanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hagg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Raikkonen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Thomas H., Jr., Bressler, Jan, Lencz, Todd, and Deary, Ian J.
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 x 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function., Errata: Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., … Deary, I. J. (2019). Author correction to Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. [Nature Communications (2018), 9, Article number 2098]. Nature Communications, 10, Article number: 2068. DOI: 10.1038/s41467-019-10160-w
Published: 2018
Full Text: View/download PDF

33. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., Ikram, M. Arfan, Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., and Ikram, M. Arfan
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
Full Text: View/download PDF

34. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., Ikram, M. Arfan, Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., and Ikram, M. Arfan
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
Full Text: View/download PDF

35. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., Ikram, M. Arfan, Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., and Ikram, M. Arfan
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
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36. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., Ikram, M. Arfan, Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., and Ikram, M. Arfan
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
Full Text: View/download PDF

37. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., Ikram, M. Arfan, Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., and Ikram, M. Arfan
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
Full Text: View/download PDF

38. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., Ikram, M. Arfan, Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., and Ikram, M. Arfan
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
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39. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P, Adams, Hieab H H, Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L, Hofer, Edith, Renteria, Miguel E, Bis, Joshua C, Arias-Vasquez, Alejandro, Ikram, M Kamran, Desrivières, Sylvane, Vernooij, Meike W, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H, Beiser, Alexa, Bernard, Manon, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chen, Qiang, Ching, Christopher R K, Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Gutman, Boris A, Hass, Johanna, Haukvik, Unn K, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N, Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liewald, David C M, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre F, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, McKay, David R, Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C, Nyquist, Paul, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, Saremi, Arvin, Satizabal, Claudia L, Schmaal, Lianne, Schork, Andrew J, Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V, Sprooten, Emma, Strike, Lachlan T, Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J, Van der Meer, Dennis, Van Donkelaar, Marjolein M J, Van Eijk, Kristel R, Van Erp, Theo G M, Van Rooij, Daan, Walton, Esther, Westlye, Lars T, Whelan, Christopher D, Windham, Beverly G, Winkler, Anderson M, Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R, Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P, Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A, Arepalli, Sampath, Assareh, Amelia A, Barral, Sandra, Bastin, Mark E, Becker, Diane M, Becker, James T, Bennett, David A, Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I, Brodaty, Henry, Brouwer, Rachel M, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Bulayeva, Kazima B, Cahn, Wiepke, Calhoun, Vince D, Cannon, Dara M, Cavalleri, Gianpiero L, Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E, Czisch, Michael, Dale, Anders M, Davies, Gareth E, De Craen, Anton J M, De Geus, Eco J C, De Jager, Philip L, De Zubicaray, Greig I, Deary, Ian J, Debette, Stéphanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C, Duggirala, Ravi, Dyer, Thomas D, Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O, Fernández, Guillén, Ferrucci, Luigi, Fisher, Simon E, Fleischman, Debra A, Ford, Ian, Fornage, Myriam, Foroud, Tatiana M, Fox, Peter T, Francks, Clyde, Fukunaga, Masaki, Gibbs, J Raphael, Glahn, David C, Gollub, Randy L, Göring, Harald H H, Green, Robert C, Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Håberg, Asta K, Hansell, Narelle K, Hardy, John, Hartman, Catharina A, Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G, Heslenfeld, Dirk J, Ho, Beng-Choon, Hoekstra, Pieter J, Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E Hulshoff, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Jönsson, Erik G, Jukema, J Wouter, Kahn, René S, Kanai, Ryota, Kloszewska, Iwona, Knopman, David S, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Lemaître, Hervé, Liu, Xinmin, Longo, Dan L, Lopez, Oscar L, Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S, McDonald, Colm, McIntosh, Andrew M, McMahon, Francis J, McMahon, Katie L, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W, Morris, Derek W, Mosley, Thomas H, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Nalls, Michael A, Nauck, Matthias, Nichols, Thomas E, Niessen, Wiro J, Nöthen, Markus M, Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L, Ophoff, Roel A, Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Pike, G Bruce, Potkin, Steven G, Psaty, Bruce M, Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L, Romanczuk-Seiferth, Nina, Rotter, Jerome I, Ryten, Mina, Sacco, Ralph L, Sachdev, Perminder S, Saykin, Andrew J, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R, Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M, Smith, Colin, Smoller, Jordan W, Soininen, Hilkka, Steen, Vidar M, Stott, David J, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G, Hernández, Maria C Valdés, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J A, Van Haren, Neeltje E M, van 't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N, Vellas, Bruno, Veltman, Dick J, Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M, Wassink, Thomas H, Weale, Michael E, Weinberger, Daniel R, Weiner, Michael W, Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y, Wright, Clinton B, Zielke, Ronald H, Zonderman, Alan B, Martin, Nicholas G, Van Duijn, Cornelia M, Wright, Margaret J, Longstreth, W T, Schumann, Gunter, Grabe, Hans J, Franke, Barbara, Launer, Lenore J, Medland, Sarah E, Seshadri, Sudha, Thompson, Paul M, Ikram, M Arfan, Hibar, Derrek P, Adams, Hieab H H, Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L, Hofer, Edith, Renteria, Miguel E, Bis, Joshua C, Arias-Vasquez, Alejandro, Ikram, M Kamran, Desrivières, Sylvane, Vernooij, Meike W, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H, Beiser, Alexa, Bernard, Manon, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chen, Qiang, Ching, Christopher R K, Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Gutman, Boris A, Hass, Johanna, Haukvik, Unn K, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N, Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liewald, David C M, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre F, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, McKay, David R, Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C, Nyquist, Paul, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, Saremi, Arvin, Satizabal, Claudia L, Schmaal, Lianne, Schork, Andrew J, Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V, Sprooten, Emma, Strike, Lachlan T, Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J, Van der Meer, Dennis, Van Donkelaar, Marjolein M J, Van Eijk, Kristel R, Van Erp, Theo G M, Van Rooij, Daan, Walton, Esther, Westlye, Lars T, Whelan, Christopher D, Windham, Beverly G, Winkler, Anderson M, Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R, Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P, Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A, Arepalli, Sampath, Assareh, Amelia A, Barral, Sandra, Bastin, Mark E, Becker, Diane M, Becker, James T, Bennett, David A, Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I, Brodaty, Henry, Brouwer, Rachel M, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Bulayeva, Kazima B, Cahn, Wiepke, Calhoun, Vince D, Cannon, Dara M, Cavalleri, Gianpiero L, Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E, Czisch, Michael, Dale, Anders M, Davies, Gareth E, De Craen, Anton J M, De Geus, Eco J C, De Jager, Philip L, De Zubicaray, Greig I, Deary, Ian J, Debette, Stéphanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C, Duggirala, Ravi, Dyer, Thomas D, Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O, Fernández, Guillén, Ferrucci, Luigi, Fisher, Simon E, Fleischman, Debra A, Ford, Ian, Fornage, Myriam, Foroud, Tatiana M, Fox, Peter T, Francks, Clyde, Fukunaga, Masaki, Gibbs, J Raphael, Glahn, David C, Gollub, Randy L, Göring, Harald H H, Green, Robert C, Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Håberg, Asta K, Hansell, Narelle K, Hardy, John, Hartman, Catharina A, Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G, Heslenfeld, Dirk J, Ho, Beng-Choon, Hoekstra, Pieter J, Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E Hulshoff, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Jönsson, Erik G, Jukema, J Wouter, Kahn, René S, Kanai, Ryota, Kloszewska, Iwona, Knopman, David S, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Lemaître, Hervé, Liu, Xinmin, Longo, Dan L, Lopez, Oscar L, Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S, McDonald, Colm, McIntosh, Andrew M, McMahon, Francis J, McMahon, Katie L, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W, Morris, Derek W, Mosley, Thomas H, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Nalls, Michael A, Nauck, Matthias, Nichols, Thomas E, Niessen, Wiro J, Nöthen, Markus M, Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L, Ophoff, Roel A, Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Pike, G Bruce, Potkin, Steven G, Psaty, Bruce M, Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L, Romanczuk-Seiferth, Nina, Rotter, Jerome I, Ryten, Mina, Sacco, Ralph L, Sachdev, Perminder S, Saykin, Andrew J, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R, Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M, Smith, Colin, Smoller, Jordan W, Soininen, Hilkka, Steen, Vidar M, Stott, David J, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G, Hernández, Maria C Valdés, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J A, Van Haren, Neeltje E M, van 't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N, Vellas, Bruno, Veltman, Dick J, Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M, Wassink, Thomas H, Weale, Michael E, Weinberger, Daniel R, Weiner, Michael W, Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y, Wright, Clinton B, Zielke, Ronald H, Zonderman, Alan B, Martin, Nicholas G, Van Duijn, Cornelia M, Wright, Margaret J, Longstreth, W T, Schumann, Gunter, Grabe, Hans J, Franke, Barbara, Launer, Lenore J, Medland, Sarah E, Seshadri, Sudha, Thompson, Paul M, and Ikram, M Arfan
Published: 2017

40. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P, Adams, Hieab H H, Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L, Hofer, Edith, Renteria, Miguel E, Bis, Joshua C, Arias-Vasquez, Alejandro, Ikram, M Kamran, Desrivières, Sylvane, Vernooij, Meike W, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H, Beiser, Alexa, Bernard, Manon, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chen, Qiang, Ching, Christopher R K, Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Gutman, Boris A, Hass, Johanna, Haukvik, Unn K, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N, Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liewald, David C M, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre F, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, McKay, David R, Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C, Nyquist, Paul, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, Saremi, Arvin, Satizabal, Claudia L, Schmaal, Lianne, Schork, Andrew J, Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V, Sprooten, Emma, Strike, Lachlan T, Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J, Van der Meer, Dennis, Van Donkelaar, Marjolein M J, Van Eijk, Kristel R, Van Erp, Theo G M, Van Rooij, Daan, Walton, Esther, Westlye, Lars T, Whelan, Christopher D, Windham, Beverly G, Winkler, Anderson M, Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R, Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P, Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A, Arepalli, Sampath, Assareh, Amelia A, Barral, Sandra, Bastin, Mark E, Becker, Diane M, Becker, James T, Bennett, David A, Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I, Brodaty, Henry, Brouwer, Rachel M, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Bulayeva, Kazima B, Cahn, Wiepke, Calhoun, Vince D, Cannon, Dara M, Cavalleri, Gianpiero L, Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E, Czisch, Michael, Dale, Anders M, Davies, Gareth E, De Craen, Anton J M, De Geus, Eco J C, De Jager, Philip L, De Zubicaray, Greig I, Deary, Ian J, Debette, Stéphanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C, Duggirala, Ravi, Dyer, Thomas D, Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O, Fernández, Guillén, Ferrucci, Luigi, Fisher, Simon E, Fleischman, Debra A, Ford, Ian, Fornage, Myriam, Foroud, Tatiana M, Fox, Peter T, Francks, Clyde, Fukunaga, Masaki, Gibbs, J Raphael, Glahn, David C, Gollub, Randy L, Göring, Harald H H, Green, Robert C, Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Håberg, Asta K, Hansell, Narelle K, Hardy, John, Hartman, Catharina A, Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G, Heslenfeld, Dirk J, Ho, Beng-Choon, Hoekstra, Pieter J, Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E Hulshoff, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Jönsson, Erik G, Jukema, J Wouter, Kahn, René S, Kanai, Ryota, Kloszewska, Iwona, Knopman, David S, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Lemaître, Hervé, Liu, Xinmin, Longo, Dan L, Lopez, Oscar L, Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S, McDonald, Colm, McIntosh, Andrew M, McMahon, Francis J, McMahon, Katie L, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W, Morris, Derek W, Mosley, Thomas H, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Nalls, Michael A, Nauck, Matthias, Nichols, Thomas E, Niessen, Wiro J, Nöthen, Markus M, Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L, Ophoff, Roel A, Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Pike, G Bruce, Potkin, Steven G, Psaty, Bruce M, Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L, Romanczuk-Seiferth, Nina, Rotter, Jerome I, Ryten, Mina, Sacco, Ralph L, Sachdev, Perminder S, Saykin, Andrew J, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R, Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M, Smith, Colin, Smoller, Jordan W, Soininen, Hilkka, Steen, Vidar M, Stott, David J, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G, Hernández, Maria C Valdés, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J A, Van Haren, Neeltje E M, van 't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N, Vellas, Bruno, Veltman, Dick J, Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M, Wassink, Thomas H, Weale, Michael E, Weinberger, Daniel R, Weiner, Michael W, Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y, Wright, Clinton B, Zielke, Ronald H, Zonderman, Alan B, Martin, Nicholas G, Van Duijn, Cornelia M, Wright, Margaret J, Longstreth, W T, Schumann, Gunter, Grabe, Hans J, Franke, Barbara, Launer, Lenore J, Medland, Sarah E, Seshadri, Sudha, Thompson, Paul M, Ikram, M Arfan, Hibar, Derrek P, Adams, Hieab H H, Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L, Hofer, Edith, Renteria, Miguel E, Bis, Joshua C, Arias-Vasquez, Alejandro, Ikram, M Kamran, Desrivières, Sylvane, Vernooij, Meike W, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H, Beiser, Alexa, Bernard, Manon, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chen, Qiang, Ching, Christopher R K, Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Gutman, Boris A, Hass, Johanna, Haukvik, Unn K, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N, Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liewald, David C M, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre F, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, McKay, David R, Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C, Nyquist, Paul, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, Saremi, Arvin, Satizabal, Claudia L, Schmaal, Lianne, Schork, Andrew J, Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V, Sprooten, Emma, Strike, Lachlan T, Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J, Van der Meer, Dennis, Van Donkelaar, Marjolein M J, Van Eijk, Kristel R, Van Erp, Theo G M, Van Rooij, Daan, Walton, Esther, Westlye, Lars T, Whelan, Christopher D, Windham, Beverly G, Winkler, Anderson M, Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R, Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P, Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A, Arepalli, Sampath, Assareh, Amelia A, Barral, Sandra, Bastin, Mark E, Becker, Diane M, Becker, James T, Bennett, David A, Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I, Brodaty, Henry, Brouwer, Rachel M, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Bulayeva, Kazima B, Cahn, Wiepke, Calhoun, Vince D, Cannon, Dara M, Cavalleri, Gianpiero L, Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E, Czisch, Michael, Dale, Anders M, Davies, Gareth E, De Craen, Anton J M, De Geus, Eco J C, De Jager, Philip L, De Zubicaray, Greig I, Deary, Ian J, Debette, Stéphanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C, Duggirala, Ravi, Dyer, Thomas D, Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O, Fernández, Guillén, Ferrucci, Luigi, Fisher, Simon E, Fleischman, Debra A, Ford, Ian, Fornage, Myriam, Foroud, Tatiana M, Fox, Peter T, Francks, Clyde, Fukunaga, Masaki, Gibbs, J Raphael, Glahn, David C, Gollub, Randy L, Göring, Harald H H, Green, Robert C, Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Håberg, Asta K, Hansell, Narelle K, Hardy, John, Hartman, Catharina A, Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G, Heslenfeld, Dirk J, Ho, Beng-Choon, Hoekstra, Pieter J, Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E Hulshoff, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Jönsson, Erik G, Jukema, J Wouter, Kahn, René S, Kanai, Ryota, Kloszewska, Iwona, Knopman, David S, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Lemaître, Hervé, Liu, Xinmin, Longo, Dan L, Lopez, Oscar L, Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S, McDonald, Colm, McIntosh, Andrew M, McMahon, Francis J, McMahon, Katie L, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W, Morris, Derek W, Mosley, Thomas H, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Nalls, Michael A, Nauck, Matthias, Nichols, Thomas E, Niessen, Wiro J, Nöthen, Markus M, Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L, Ophoff, Roel A, Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Pike, G Bruce, Potkin, Steven G, Psaty, Bruce M, Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L, Romanczuk-Seiferth, Nina, Rotter, Jerome I, Ryten, Mina, Sacco, Ralph L, Sachdev, Perminder S, Saykin, Andrew J, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R, Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M, Smith, Colin, Smoller, Jordan W, Soininen, Hilkka, Steen, Vidar M, Stott, David J, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G, Hernández, Maria C Valdés, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J A, Van Haren, Neeltje E M, van 't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N, Vellas, Bruno, Veltman, Dick J, Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M, Wassink, Thomas H, Weale, Michael E, Weinberger, Daniel R, Weiner, Michael W, Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y, Wright, Clinton B, Zielke, Ronald H, Zonderman, Alan B, Martin, Nicholas G, Van Duijn, Cornelia M, Wright, Margaret J, Longstreth, W T, Schumann, Gunter, Grabe, Hans J, Franke, Barbara, Launer, Lenore J, Medland, Sarah E, Seshadri, Sudha, Thompson, Paul M, and Ikram, M Arfan
Published: 2017

41. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P, Adams, Hieab H H, Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L, Hofer, Edith, Renteria, Miguel E, Bis, Joshua C, Arias-Vasquez, Alejandro, Ikram, M Kamran, Desrivières, Sylvane, Vernooij, Meike W, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H, Beiser, Alexa, Bernard, Manon, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chen, Qiang, Ching, Christopher R K, Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Gutman, Boris A, Hass, Johanna, Haukvik, Unn K, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N, Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liewald, David C M, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre F, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, McKay, David R, Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C, Nyquist, Paul, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, Saremi, Arvin, Satizabal, Claudia L, Schmaal, Lianne, Schork, Andrew J, Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V, Sprooten, Emma, Strike, Lachlan T, Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J, Van der Meer, Dennis, Van Donkelaar, Marjolein M J, Van Eijk, Kristel R, Van Erp, Theo G M, Van Rooij, Daan, Walton, Esther, Westlye, Lars T, Whelan, Christopher D, Windham, Beverly G, Winkler, Anderson M, Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R, Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P, Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A, Arepalli, Sampath, Assareh, Amelia A, Barral, Sandra, Bastin, Mark E, Becker, Diane M, Becker, James T, Bennett, David A, Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I, Brodaty, Henry, Brouwer, Rachel M, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Bulayeva, Kazima B, Cahn, Wiepke, Calhoun, Vince D, Cannon, Dara M, Cavalleri, Gianpiero L, Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E, Czisch, Michael, Dale, Anders M, Davies, Gareth E, De Craen, Anton J M, De Geus, Eco J C, De Jager, Philip L, De Zubicaray, Greig I, Deary, Ian J, Debette, Stéphanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C, Duggirala, Ravi, Dyer, Thomas D, Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O, Fernández, Guillén, Ferrucci, Luigi, Fisher, Simon E, Fleischman, Debra A, Ford, Ian, Fornage, Myriam, Foroud, Tatiana M, Fox, Peter T, Francks, Clyde, Fukunaga, Masaki, Gibbs, J Raphael, Glahn, David C, Gollub, Randy L, Göring, Harald H H, Green, Robert C, Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Håberg, Asta K, Hansell, Narelle K, Hardy, John, Hartman, Catharina A, Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G, Heslenfeld, Dirk J, Ho, Beng-Choon, Hoekstra, Pieter J, Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E Hulshoff, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Jönsson, Erik G, Jukema, J Wouter, Kahn, René S, Kanai, Ryota, Kloszewska, Iwona, Knopman, David S, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Lemaître, Hervé, Liu, Xinmin, Longo, Dan L, Lopez, Oscar L, Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S, McDonald, Colm, McIntosh, Andrew M, McMahon, Francis J, McMahon, Katie L, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W, Morris, Derek W, Mosley, Thomas H, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Nalls, Michael A, Nauck, Matthias, Nichols, Thomas E, Niessen, Wiro J, Nöthen, Markus M, Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L, Ophoff, Roel A, Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Pike, G Bruce, Potkin, Steven G, Psaty, Bruce M, Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L, Romanczuk-Seiferth, Nina, Rotter, Jerome I, Ryten, Mina, Sacco, Ralph L, Sachdev, Perminder S, Saykin, Andrew J, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R, Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M, Smith, Colin, Smoller, Jordan W, Soininen, Hilkka, Steen, Vidar M, Stott, David J, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G, Hernández, Maria C Valdés, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J A, Van Haren, Neeltje E M, van 't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N, Vellas, Bruno, Veltman, Dick J, Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M, Wassink, Thomas H, Weale, Michael E, Weinberger, Daniel R, Weiner, Michael W, Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y, Wright, Clinton B, Zielke, Ronald H, Zonderman, Alan B, Martin, Nicholas G, Van Duijn, Cornelia M, Wright, Margaret J, Longstreth, W T, Schumann, Gunter, Grabe, Hans J, Franke, Barbara, Launer, Lenore J, Medland, Sarah E, Seshadri, Sudha, Thompson, Paul M, Ikram, M Arfan, Hibar, Derrek P, Adams, Hieab H H, Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L, Hofer, Edith, Renteria, Miguel E, Bis, Joshua C, Arias-Vasquez, Alejandro, Ikram, M Kamran, Desrivières, Sylvane, Vernooij, Meike W, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H, Beiser, Alexa, Bernard, Manon, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chen, Qiang, Ching, Christopher R K, Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Gutman, Boris A, Hass, Johanna, Haukvik, Unn K, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N, Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liewald, David C M, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre F, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, McKay, David R, Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C, Nyquist, Paul, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, Saremi, Arvin, Satizabal, Claudia L, Schmaal, Lianne, Schork, Andrew J, Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V, Sprooten, Emma, Strike, Lachlan T, Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J, Van der Meer, Dennis, Van Donkelaar, Marjolein M J, Van Eijk, Kristel R, Van Erp, Theo G M, Van Rooij, Daan, Walton, Esther, Westlye, Lars T, Whelan, Christopher D, Windham, Beverly G, Winkler, Anderson M, Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R, Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P, Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A, Arepalli, Sampath, Assareh, Amelia A, Barral, Sandra, Bastin, Mark E, Becker, Diane M, Becker, James T, Bennett, David A, Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I, Brodaty, Henry, Brouwer, Rachel M, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Bulayeva, Kazima B, Cahn, Wiepke, Calhoun, Vince D, Cannon, Dara M, Cavalleri, Gianpiero L, Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E, Czisch, Michael, Dale, Anders M, Davies, Gareth E, De Craen, Anton J M, De Geus, Eco J C, De Jager, Philip L, De Zubicaray, Greig I, Deary, Ian J, Debette, Stéphanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C, Duggirala, Ravi, Dyer, Thomas D, Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O, Fernández, Guillén, Ferrucci, Luigi, Fisher, Simon E, Fleischman, Debra A, Ford, Ian, Fornage, Myriam, Foroud, Tatiana M, Fox, Peter T, Francks, Clyde, Fukunaga, Masaki, Gibbs, J Raphael, Glahn, David C, Gollub, Randy L, Göring, Harald H H, Green, Robert C, Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Håberg, Asta K, Hansell, Narelle K, Hardy, John, Hartman, Catharina A, Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G, Heslenfeld, Dirk J, Ho, Beng-Choon, Hoekstra, Pieter J, Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E Hulshoff, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Jönsson, Erik G, Jukema, J Wouter, Kahn, René S, Kanai, Ryota, Kloszewska, Iwona, Knopman, David S, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Lemaître, Hervé, Liu, Xinmin, Longo, Dan L, Lopez, Oscar L, Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S, McDonald, Colm, McIntosh, Andrew M, McMahon, Francis J, McMahon, Katie L, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W, Morris, Derek W, Mosley, Thomas H, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Nalls, Michael A, Nauck, Matthias, Nichols, Thomas E, Niessen, Wiro J, Nöthen, Markus M, Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L, Ophoff, Roel A, Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Pike, G Bruce, Potkin, Steven G, Psaty, Bruce M, Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L, Romanczuk-Seiferth, Nina, Rotter, Jerome I, Ryten, Mina, Sacco, Ralph L, Sachdev, Perminder S, Saykin, Andrew J, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R, Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M, Smith, Colin, Smoller, Jordan W, Soininen, Hilkka, Steen, Vidar M, Stott, David J, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G, Hernández, Maria C Valdés, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J A, Van Haren, Neeltje E M, van 't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N, Vellas, Bruno, Veltman, Dick J, Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M, Wassink, Thomas H, Weale, Michael E, Weinberger, Daniel R, Weiner, Michael W, Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y, Wright, Clinton B, Zielke, Ronald H, Zonderman, Alan B, Martin, Nicholas G, Van Duijn, Cornelia M, Wright, Margaret J, Longstreth, W T, Schumann, Gunter, Grabe, Hans J, Franke, Barbara, Launer, Lenore J, Medland, Sarah E, Seshadri, Sudha, Thompson, Paul M, and Ikram, M Arfan
Published: 2017

42. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivières, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Sämann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stéphanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernández, Guillén, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Göring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Håberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Hulshoff Pol, Hilleke E., Ikeda, Masashi, Jack Jr, Clifford R., Jenkinson, Mark, Johnson, Robert, Jönsson, Erik G., Jukema, J. Wouter, Kahn, René S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaître, Hervé, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Mühleisen, Thomas W., Müller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nöthen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernández, Maria C. Valdés, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van ’t Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., Ikram, M. Arfan, Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivières, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Sämann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stéphanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernández, Guillén, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Göring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Håberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Hulshoff Pol, Hilleke E., Ikeda, Masashi, Jack Jr, Clifford R., Jenkinson, Mark, Johnson, Robert, Jönsson, Erik G., Jukema, J. Wouter, Kahn, René S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaître, Hervé, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Mühleisen, Thomas W., Müller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nöthen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernández, Maria C. Valdés, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van ’t Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., and Ikram, M. Arfan
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease ((rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017

43. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivières, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Sämann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stéphanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernández, Guillén, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Göring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Håberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Hulshoff Pol, Hilleke E., Ikeda, Masashi, Jack Jr, Clifford R., Jenkinson, Mark, Johnson, Robert, Jönsson, Erik G., Jukema, J. Wouter, Kahn, René S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaître, Hervé, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Mühleisen, Thomas W., Müller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nöthen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernández, Maria C. Valdés, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van ’t Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., Ikram, M. Arfan, Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivières, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Sämann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stéphanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernández, Guillén, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Göring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Håberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Hulshoff Pol, Hilleke E., Ikeda, Masashi, Jack Jr, Clifford R., Jenkinson, Mark, Johnson, Robert, Jönsson, Erik G., Jukema, J. Wouter, Kahn, René S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaître, Hervé, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Mühleisen, Thomas W., Müller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nöthen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernández, Maria C. Valdés, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van ’t Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., and Ikram, M. Arfan
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease ((rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017

44. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., Ikram, M. Arfan, Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., and Ikram, M. Arfan
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
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45. Genetic influences on individual differences in longitudinal changes in global and subcortical brain volumes: Results of the ENIGMA plasticity working group

Author: Brouwer, Rachel M, Panizzon, Matthew S, Glahn, David C, Hibar, Derrek P, Hua, Xue, Jahanshad, Neda, Abramovic, Lucija, De Zubicaray, Greig I, Franz, Carol E, Hansell, Narelle K, Hickie, Ian B, Koenis, Marinka M G, Martin, Nicholas G, Mather, Karen A, McMahon, Katie L, Schnack, Hugo G, Strike, Lachlan T, Swagerman, Suzanne C, Thalamuthu, Anbupalam, Wen, Wei, Gilmore, John H, Gogtay, Nitin, Kahn, René S, Sachdev, Perminder S, Wright, Margaret J, Boomsma, Dorret I, Kremen, William S, Thompson, Paul M, Hulshoff Pol, Hilleke E, Brouwer, Rachel M, Panizzon, Matthew S, Glahn, David C, Hibar, Derrek P, Hua, Xue, Jahanshad, Neda, Abramovic, Lucija, De Zubicaray, Greig I, Franz, Carol E, Hansell, Narelle K, Hickie, Ian B, Koenis, Marinka M G, Martin, Nicholas G, Mather, Karen A, McMahon, Katie L, Schnack, Hugo G, Strike, Lachlan T, Swagerman, Suzanne C, Thalamuthu, Anbupalam, Wen, Wei, Gilmore, John H, Gogtay, Nitin, Kahn, René S, Sachdev, Perminder S, Wright, Margaret J, Boomsma, Dorret I, Kremen, William S, Thompson, Paul M, and Hulshoff Pol, Hilleke E
Abstract: Structural brain changes that occur during development and ageing are related to mental health and general cognitive functioning. Individuals differ in the extent to which their brain volumes change over time, but whether these differences can be attributed to differences in their genotypes has not been widely studied. Here we estimate heritability (h(2) ) of changes in global and subcortical brain volumes in five longitudinal twin cohorts from across the world and in different stages of the lifespan (N = 861). Heritability estimates of brain changes were significant and ranged from 16% (caudate) to 42% (cerebellar gray matter) for all global and most subcortical volumes (with the exception of thalamus and pallidum). Heritability estimates of change rates were generally higher in adults than in children suggesting an increasing influence of genetic factors explaining individual differences in brain structural changes with age. In children, environmental influences in part explained individual differences in developmental changes in brain structure. Multivariate genetic modeling showed that genetic influences of change rates and baseline volume significantly overlapped for many structures. The genetic influences explaining individual differences in the change rate for cerebellum, cerebellar gray matter and lateral ventricles were independent of the genetic influences explaining differences in their baseline volumes. These results imply the existence of genetic variants that are specific for brain plasticity, rather than brain volume itself. Identifying these genes may increase our understanding of brain development and ageing and possibly have implications for diseases that are characterized by deviant developmental trajectories of brain structure. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
Published: 2017
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46. Novel genetic loci associated with hippocampal volume

Author: ZL Cerebrovasculaire Ziekten Medisch, Onderzoeksgroep 4, Brain, Psychologen i.o., Onderzoeksgroep 2, Neurogenetica, Onderzoeksgroep 1, Affectieve & Psychotische Med., Onderzoek, Hibar, Derrek P, Adams, Hieab H H, Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L, Hofer, Edith, Renteria, Miguel E, Bis, Joshua C, Arias-Vasquez, Alejandro, Ikram, M Kamran, Desrivières, Sylvane, Vernooij, Meike W, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H, Beiser, Alexa, Bernard, Manon, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chen, Qiang, Ching, Christopher R K, Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Gutman, Boris A, Hass, Johanna, Haukvik, Unn K, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N, Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liewald, David C M, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre F, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, McKay, David R, Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C, Nyquist, Paul, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, Saremi, Arvin, Satizabal, Claudia L, Schmaal, Lianne, Schork, Andrew J, Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V, Sprooten, Emma, Strike, Lachlan T, Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J, Van der Meer, Dennis, Van Donkelaar, Marjolein M J, Van Eijk, Kristel R, Van Erp, Theo G M, Van Rooij, Daan, Walton, Esther, Westlye, Lars T, Whelan, Christopher D, Windham, Beverly G, Winkler, Anderson M, Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R, Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P, Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A, Arepalli, Sampath, Assareh, Amelia A, Barral, Sandra, Bastin, Mark E, Becker, Diane M, Becker, James T, Bennett, David A, Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I, Brodaty, Henry, Brouwer, Rachel M, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Bulayeva, Kazima B, Cahn, Wiepke, Calhoun, Vince D, Cannon, Dara M, Cavalleri, Gianpiero L, Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E, Czisch, Michael, Dale, Anders M, Davies, Gareth E, De Craen, Anton J M, De Geus, Eco J C, De Jager, Philip L, De Zubicaray, Greig I, Deary, Ian J, Debette, Stéphanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C, Duggirala, Ravi, Dyer, Thomas D, Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O, Fernández, Guillén, Ferrucci, Luigi, Fisher, Simon E, Fleischman, Debra A, Ford, Ian, Fornage, Myriam, Foroud, Tatiana M, Fox, Peter T, Francks, Clyde, Fukunaga, Masaki, Gibbs, J Raphael, Glahn, David C, Gollub, Randy L, Göring, Harald H H, Green, Robert C, Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Håberg, Asta K, Hansell, Narelle K, Hardy, John, Hartman, Catharina A, Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G, Heslenfeld, Dirk J, Ho, Beng-Choon, Hoekstra, Pieter J, Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E Hulshoff, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Jönsson, Erik G, Jukema, J Wouter, Kahn, René S, Kanai, Ryota, Kloszewska, Iwona, Knopman, David S, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Lemaître, Hervé, Liu, Xinmin, Longo, Dan L, Lopez, Oscar L, Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S, McDonald, Colm, McIntosh, Andrew M, McMahon, Francis J, McMahon, Katie L, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W, Morris, Derek W, Mosley, Thomas H, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Nalls, Michael A, Nauck, Matthias, Nichols, Thomas E, Niessen, Wiro J, Nöthen, Markus M, Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L, Ophoff, Roel A, Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Pike, G Bruce, Potkin, Steven G, Psaty, Bruce M, Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L, Romanczuk-Seiferth, Nina, Rotter, Jerome I, Ryten, Mina, Sacco, Ralph L, Sachdev, Perminder S, Saykin, Andrew J, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R, Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M, Smith, Colin, Smoller, Jordan W, Soininen, Hilkka, Steen, Vidar M, Stott, David J, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G, Hernández, Maria C Valdés, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J A, Van Haren, Neeltje E M, van 't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N, Vellas, Bruno, Veltman, Dick J, Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M, Wassink, Thomas H, Weale, Michael E, Weinberger, Daniel R, Weiner, Michael W, Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y, Wright, Clinton B, Zielke, Ronald H, Zonderman, Alan B, Martin, Nicholas G, Van Duijn, Cornelia M, Wright, Margaret J, Longstreth, W T, Schumann, Gunter, Grabe, Hans J, Franke, Barbara, Launer, Lenore J, Medland, Sarah E, Seshadri, Sudha, Thompson, Paul M, Ikram, M Arfan, ZL Cerebrovasculaire Ziekten Medisch, Onderzoeksgroep 4, Brain, Psychologen i.o., Onderzoeksgroep 2, Neurogenetica, Onderzoeksgroep 1, Affectieve & Psychotische Med., Onderzoek, Hibar, Derrek P, Adams, Hieab H H, Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L, Hofer, Edith, Renteria, Miguel E, Bis, Joshua C, Arias-Vasquez, Alejandro, Ikram, M Kamran, Desrivières, Sylvane, Vernooij, Meike W, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H, Beiser, Alexa, Bernard, Manon, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chen, Qiang, Ching, Christopher R K, Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Gutman, Boris A, Hass, Johanna, Haukvik, Unn K, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N, Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liewald, David C M, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre F, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, McKay, David R, Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C, Nyquist, Paul, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, Saremi, Arvin, Satizabal, Claudia L, Schmaal, Lianne, Schork, Andrew J, Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V, Sprooten, Emma, Strike, Lachlan T, Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J, Van der Meer, Dennis, Van Donkelaar, Marjolein M J, Van Eijk, Kristel R, Van Erp, Theo G M, Van Rooij, Daan, Walton, Esther, Westlye, Lars T, Whelan, Christopher D, Windham, Beverly G, Winkler, Anderson M, Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R, Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P, Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A, Arepalli, Sampath, Assareh, Amelia A, Barral, Sandra, Bastin, Mark E, Becker, Diane M, Becker, James T, Bennett, David A, Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I, Brodaty, Henry, Brouwer, Rachel M, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Bulayeva, Kazima B, Cahn, Wiepke, Calhoun, Vince D, Cannon, Dara M, Cavalleri, Gianpiero L, Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E, Czisch, Michael, Dale, Anders M, Davies, Gareth E, De Craen, Anton J M, De Geus, Eco J C, De Jager, Philip L, De Zubicaray, Greig I, Deary, Ian J, Debette, Stéphanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C, Duggirala, Ravi, Dyer, Thomas D, Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O, Fernández, Guillén, Ferrucci, Luigi, Fisher, Simon E, Fleischman, Debra A, Ford, Ian, Fornage, Myriam, Foroud, Tatiana M, Fox, Peter T, Francks, Clyde, Fukunaga, Masaki, Gibbs, J Raphael, Glahn, David C, Gollub, Randy L, Göring, Harald H H, Green, Robert C, Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Håberg, Asta K, Hansell, Narelle K, Hardy, John, Hartman, Catharina A, Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G, Heslenfeld, Dirk J, Ho, Beng-Choon, Hoekstra, Pieter J, Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E Hulshoff, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Jönsson, Erik G, Jukema, J Wouter, Kahn, René S, Kanai, Ryota, Kloszewska, Iwona, Knopman, David S, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Lemaître, Hervé, Liu, Xinmin, Longo, Dan L, Lopez, Oscar L, Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S, McDonald, Colm, McIntosh, Andrew M, McMahon, Francis J, McMahon, Katie L, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W, Morris, Derek W, Mosley, Thomas H, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Nalls, Michael A, Nauck, Matthias, Nichols, Thomas E, Niessen, Wiro J, Nöthen, Markus M, Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L, Ophoff, Roel A, Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Pike, G Bruce, Potkin, Steven G, Psaty, Bruce M, Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L, Romanczuk-Seiferth, Nina, Rotter, Jerome I, Ryten, Mina, Sacco, Ralph L, Sachdev, Perminder S, Saykin, Andrew J, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R, Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M, Smith, Colin, Smoller, Jordan W, Soininen, Hilkka, Steen, Vidar M, Stott, David J, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G, Hernández, Maria C Valdés, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J A, Van Haren, Neeltje E M, van 't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N, Vellas, Bruno, Veltman, Dick J, Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M, Wassink, Thomas H, Weale, Michael E, Weinberger, Daniel R, Weiner, Michael W, Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y, Wright, Clinton B, Zielke, Ronald H, Zonderman, Alan B, Martin, Nicholas G, Van Duijn, Cornelia M, Wright, Margaret J, Longstreth, W T, Schumann, Gunter, Grabe, Hans J, Franke, Barbara, Launer, Lenore J, Medland, Sarah E, Seshadri, Sudha, Thompson, Paul M, and Ikram, M Arfan
Published: 2017

47. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., Ikram, M. Arfan, Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., and Ikram, M. Arfan
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
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48. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., Ikram, M. Arfan, Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., and Ikram, M. Arfan
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
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49. Novel genetic loci associated with hippocampal volume

Author: Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., Ikram, M. Arfan, Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F., Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Maniega, Susana Munoz, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Puetz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Saemann, Philipp G., Saremi, Arvin, Satizabal, Claudia L., Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van der Grond, Jeroen, Van der Lee, Sven J., Van der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, DeCarli, Charles, Delanty, Norman, Depondt, Chantal, DeStefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jr., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van der Brug, Marcel, van der Lugt, Aad, van der Wee, Nic J. A., Van Haren, Neeltje E. M., van't Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Voelzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M., and Ikram, M. Arfan
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
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50. Hair cortisol in twins: heritability and genetic overlap with psychological variables and stress-system genes

Author: Rietschel, Liz, Streit, Fabian, Zhu, Gu, McAloney, Kerrie, Frank, Josef, Couvy-Duchesne, Baptiste, Witt, Stephanie H; https://orcid.org/0000-0002-1571-1468, Binz, Tina M; https://orcid.org/0000-0001-6783-1202, McGrath, John, Hickie, Ian B, Hansell, Narelle K, Wright, Margaret J, Gillespie, Nathan A, Forstner, Andreas J, Schulze, Thomas G, Wüst, Stefan, Nöthen, Markus M, Baumgartner, Markus R; https://orcid.org/0000-0002-0979-931X, Walker, Brian R, Crawford, Andrew A, Colodro-Conde, Lucía; https://orcid.org/0000-0002-9004-364X, Medland, Sarah E, Martin, Nicholas G, Rietschel, Marcella, Rietschel, Liz, Streit, Fabian, Zhu, Gu, McAloney, Kerrie, Frank, Josef, Couvy-Duchesne, Baptiste, Witt, Stephanie H; https://orcid.org/0000-0002-1571-1468, Binz, Tina M; https://orcid.org/0000-0001-6783-1202, McGrath, John, Hickie, Ian B, Hansell, Narelle K, Wright, Margaret J, Gillespie, Nathan A, Forstner, Andreas J, Schulze, Thomas G, Wüst, Stefan, Nöthen, Markus M, Baumgartner, Markus R; https://orcid.org/0000-0002-0979-931X, Walker, Brian R, Crawford, Andrew A, Colodro-Conde, Lucía; https://orcid.org/0000-0002-9004-364X, Medland, Sarah E, Martin, Nicholas G, and Rietschel, Marcella
Abstract: Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.
Published: 2017

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