938 results on '"Pers, Tune H."'
Search Results
2. GLP-1-directed NMDA receptor antagonism for obesity treatment
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Petersen, Jonas, Ludwig, Mette Q., Juozaityte, Vaida, Ranea-Robles, Pablo, Svendsen, Charlotte, Hwang, Eunsang, Kristensen, Amalie W., Fadahunsi, Nicole, Lund, Jens, Breum, Alberte W., Mathiesen, Cecilie V., Sachs, Luisa, Moreno-Justicia, Roger, Rohlfs, Rebecca, Ford, James C., Douros, Jonathan D., Finan, Brian, Portillo, Bryan, Grose, Kyle, Petersen, Jacob E., Trauelsen, Mette, Feuchtinger, Annette, DiMarchi, Richard D., Schwartz, Thue W., Deshmukh, Atul S., Thomsen, Morten B., Kohlmeier, Kristi A., Williams, Kevin W., Pers, Tune H., Frølund, Bente, Strømgaard, Kristian, Klein, Anders B., and Clemmensen, Christoffer
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- 2024
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3. GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification
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Lagou, Vasiliki, Jiang, Longda, Ulrich, Anna, Zudina, Liudmila, González, Karla Sofia Gutiérrez, Balkhiyarova, Zhanna, Faggian, Alessia, Maina, Jared G., Chen, Shiqian, Todorov, Petar V., Sharapov, Sodbo, David, Alessia, Marullo, Letizia, Mägi, Reedik, Rujan, Roxana-Maria, Ahlqvist, Emma, Thorleifsson, Gudmar, Gao, Ηe, Εvangelou, Εvangelos, Benyamin, Beben, Scott, Robert A., Isaacs, Aaron, Zhao, Jing Hua, Willems, Sara M., Johnson, Toby, Gieger, Christian, Grallert, Harald, Meisinger, Christa, Müller-Nurasyid, Martina, Strawbridge, Rona J., Goel, Anuj, Rybin, Denis, Albrecht, Eva, Jackson, Anne U., Stringham, Heather M., Corrêa, Jr., Ivan R., Farber-Eger, Eric, Steinthorsdottir, Valgerdur, Uitterlinden, André G., Munroe, Patricia B., Brown, Morris J., Schmidberger, Julian, Holmen, Oddgeir, Thorand, Barbara, Hveem, Kristian, Wilsgaard, Tom, Mohlke, Karen L., Wang, Zhe, Shmeliov, Aleksey, den Hoed, Marcel, Loos, Ruth J. F., Kratzer, Wolfgang, Haenle, Mark, Koenig, Wolfgang, Boehm, Bernhard O., Tan, Tricia M., Tomas, Alejandra, Salem, Victoria, Barroso, Inês, Tuomilehto, Jaakko, Boehnke, Michael, Florez, Jose C., Hamsten, Anders, Watkins, Hugh, Njølstad, Inger, Wichmann, H.-Erich, Caulfield, Mark J., Khaw, Kay-Tee, van Duijn, Cornelia M., Hofman, Albert, Wareham, Nicholas J., Langenberg, Claudia, Whitfield, John B., Martin, Nicholas G., Montgomery, Grant, Scapoli, Chiara, Tzoulaki, Ioanna, Elliott, Paul, Thorsteinsdottir, Unnur, Stefansson, Kari, Brittain, Evan L., McCarthy, Mark I., Froguel, Philippe, Sexton, Patrick M., Wootten, Denise, Groop, Leif, Dupuis, Josée, Meigs, James B., Deganutti, Giuseppe, Demirkan, Ayse, Pers, Tune H., Reynolds, Christopher A., Aulchenko, Yurii S., Kaakinen, Marika A., Jones, Ben, and Prokopenko, Inga
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- 2023
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4. Assessing household lifestyle exposures from consumer purchases, the My Purchases cohort
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Møller, Frederik T., Junker, Thor Grønborg, Kold Sørensen, Kathrine, Eves, Caroline, Wohlfahrt, Jan, Dillner, Joakim, Torp-Pedersen, Christian, Wilkowski, Bartlomiej, Chong, Steven, Pers, Tune H., Yakimov, Victor, Müller, Heimo, Ethelberg, Steen, and Melbye, Mads
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- 2023
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5. Adipogenic and SWAT cells separate from a common progenitor in human brown and white adipose depots
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Palani, Nagendra P., Horvath, Carla, Timshel, Pascal N., Folkertsma, Pytrik, Grønning, Alexander G. B., Henriksen, Tora I., Peijs, Lone, Jensen, Verena H., Sun, Wenfei, Jespersen, Naja Z., Wolfrum, Christian, Pers, Tune H., Nielsen, Søren, and Scheele, Camilla
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- 2023
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6. Hypothalamic hormone-sensitive lipase regulates appetite and energy homeostasis
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Hundahl, Cecilie, Kotzbeck, Petra, Burm, Hayley B, Christiansen, Søren H, Torz, Lola, Helge, Aske W, Madsen, Martin P, Ratner, Cecilia, Serup, Annette K, Thompson, Jonatan J, Eichmann, Thomas O, Pers, Tune H, Woldbye, David PD, Piomelli, Daniele, Kiens, Bente, Zechner, Rudolf, Skov, Louise J, and Holst, Birgitte
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Biochemistry and Cell Biology ,Biological Sciences ,Neurosciences ,Nutrition ,Obesity ,Oral and gastrointestinal ,Cardiovascular ,Cancer ,Stroke ,Metabolic and endocrine ,Agouti-Related Protein ,Animals ,Appetite ,Body Weight ,Diet ,High-Fat ,Eating ,Energy Metabolism ,Female ,Homeostasis ,Hyperphagia ,Hypothalamus ,Male ,Mice ,Mice ,Inbred C57BL ,Mice ,Knockout ,Neurons ,Neuropeptide Y ,RNA Splicing Factors ,Sterol Esterase ,Stress ,Physiological ,Transcriptome ,Appetite regulation ,Stress ,Physiology ,Biochemistry and cell biology - Abstract
ObjectiveThe goal of this study was to investigate the importance of central hormone-sensitive lipase (HSL) expression in the regulation of food intake and body weight in mice to clarify whether intracellular lipolysis in the mammalian hypothalamus plays a role in regulating appetite.MethodsUsing pharmacological and genetic approaches, we investigated the role of HSL in the rodent brain in the regulation of feeding and energy homeostasis under basal conditions during acute stress and high-fat diet feeding.ResultsWe found that HSL, a key enzyme in the catabolism of cellular lipid stores, is expressed in the appetite-regulating centers in the hypothalamus and is activated by acute stress through a mechanism similar to that observed in adipose tissue and skeletal muscle. Inhibition of HSL in rodent models by a synthetic ligand, global knockout, or brain-specific deletion of HSL prevents a decrease in food intake normally seen in response to acute stress and is associated with the increased expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related peptide (AgRP). Increased food intake can be reversed by adeno-associated virus-mediated reintroduction of HSL in neurons of the mediobasal hypothalamus. Importantly, metabolic stress induced by a high-fat diet also enhances the hyperphagic phenotype of HSL-deficient mice. Specific deletion of HSL in the ventromedial hypothalamic nucleus (VMH) or AgRP neurons reveals that HSL in the VMH plays a role in both acute stress-induced food intake and high-fat diet-induced obesity.ConclusionsOur results indicate that HSL activity in the mediobasal hypothalamus is involved in the acute reduction in food intake during the acute stress response and sensing of a high-fat diet.
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- 2021
7. Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions
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Marshall, Christian R., Merico, Daniele, Thiruvahindrapuram, Bhooma, Wang, Zhouzhi, Scherer, Stephen W., Howrigan, Daniel P, Ripke, Stephan, Bulik-Sullivan, Brendan, Farh, Kai-How, Fromer, Menachem, Goldstein, Jacqueline I., Huang, Hailiang, Lee, Phil, Daly, Mark J., Neale, Benjamin M., Belliveau, Richard A., Jr., Bergen, Sarah E., Bevilacqua, Elizabeth, Chambert, Kimberley D., O'Dushlaine, Colm, Scolnick, Edward M., Smoller, Jordan W., Moran, Jennifer L., Palotie, Aarno, Petryshen, Tracey L., Wu, Wenting, Greer, Douglas S., Antaki, Danny, Shetty, Aniket, Gujral, Madhusudan, Brandler, William M., Malhotra, Dheeraj, Fuentes Fajarado, Karin V., Maile, Michelle S., Holmans, Peter A., Carrera, Noa, Craddock, Nick, Escott-Price, Valentina, Georgieva, Lyudmila, Hamshere, Marian L., Kavanagh, David, Legge, Sophie E., Pocklington, Andrew J., Richards, Alexander L., Ruderfer, Douglas M., Williams, Nigel M., Kirov, George, Owen, Michael J., Pinto, Dalila, Cai, Guiqing, Davis, Kenneth L., Drapeau, Elodie, Friedman, Joseph I, Haroutunian, Vahram, Parkhomenko, Elena, Reichenberg, Abraham, Silverman, Jeremy M., Buxbaum, Joseph D., Domenici, Enrico, Agartz, Ingrid, Djurovic, Srdjan, Mattingsdal, Morten, Melle, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Söderman, Erik, Albus, Margot, Alexander, Madeline, Laurent, Claudine, Levinson, Douglas F., Amin, Farooq, Atkins, Joshua, Cairns, Murray J., Scott, Rodney J., Tooney, Paul A., Wu, Jing Qin, Bacanu, Silviu A., Bigdeli, Tim B., Reimers, Mark A., Webb, Bradley T., Wolen, Aaron R., Wormley, Brandon K., Kendler, Kenneth S., Riley, Brien P., Kähler, Anna K., Magnusson, Patrik K.E., Hultman, Christina M., Bertalan, Marcelo, Hansen, Thomas, Olsen, Line, Rasmussen, Henrik B., Werge, Thomas, Mattheisen, Manuel, Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Roffman, Joshua L., Byerley, William, Cahn, Wiepke, Kahn, René S, Strengman, Eric, Ophoff, Roel A., Carr, Vaughan J., Catts, Stanley V., Henskens, Frans A., Loughland, Carmel M., Michie, Patricia T., Pantelis, Christos, Schall, Ulrich, Jablensky, Assen V., Kelly, Brian J., Campion, Dominique, Cantor, Rita M., Cheng, Wei, Cloninger, C. Robert, Svrakic, Dragan M, Cohen, David, Cormican, Paul, Donohoe, Gary, Morris, Derek W., Corvin, Aiden, Gill, Michael, Crespo-Facorro, Benedicto, Crowley, James J., Farrell, Martilias S., Giusti-Rodríguez, Paola, Kim, Yunjung, Szatkiewicz, Jin P., Williams, Stephanie, Curtis, David, Pimm, Jonathan, Gurling, Hugh, McQuillin, Andrew, Davidson, Michael, Weiser, Mark, Degenhardt, Franziska, Forstner, Andreas J., Herms, Stefan, Hoffmann, Per, Hofman, Andrea, Cichon, Sven, Nöthen, Markus M., Del Favero, Jurgen, DeLisi, Lynn E., McCarley, Robert W., Levy, Deborah L., Mesholam-Gately, Raquelle I., Seidman, Larry J., Dikeos, Dimitris, Papadimitriou, George N., Dinan, Timothy, Duan, Jubao, Sanders, Alan R., Gejman, Pablo V., Gershon, Elliot S., Dudbridge, Frank, Eichhammer, Peter, Eriksson, Johan, Salomaa, Veikko, Essioux, Laurent, Fanous, Ayman H., Knowles, James A., Pato, Michele T., Pato, Carlos N., Frank, Josef, Meier, Sandra, Schulze, Thomas G., Strohmaier, Jana, Witt, Stephanie H., Rietschel, Marcella, Franke, Lude, Karjalainen, Juha, Freedman, Robert, Olincy, Ann, Freimer, Nelson B., Purcell, Shaun M., Roussos, Panos, Stahl, Eli A., Sklar, Pamela, Giegling, Ina, Hartmann, Annette M., Konte, Bettina, Rujescu, Dan, Godard, Stephanie, Hirschhorn, Joel N., Pers, Tune H., Price, Alkes, Esko, Tõnu, Gratten, Jacob, Lee, S. Hong, Visscher, Peter M., Wray, Naomi R., Mowry, Bryan J., de Haan, Lieuwe, Meijer, Carin J., Hansen, Mark, Ikeda, Masashi, Iwata, Nakao, Joa, Inge, Kalaydjieva, Luba, Keller, Matthew C., Kennedy, James L., Zai, Clement C., Knight, Jo, Lerer, Bernard, Liang, Kung-Yee, Lieberman, Jeffrey, Stroup, T. Scott, Lönnqvist, Jouko, Suvisaari, Jaana, Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, McDonald, Colm, McIntosh, Andrew M., Blackwood, Douglas H.R., Metspalu, Andres, Milani, Lili, Milanova, Vihra, Mokrab, Younes, Collier, David A., Müller-Myhsok, Bertram, Murphy, Kieran C., Murray, Robin M., Powell, John, Myin-Germeys, Inez, Van Os, Jim, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Pulver, Ann E., Nicodemus, Kristin K., Nisenbaum, Laura, Nordin, Annelie, Adolfsson, Rolf, O'Callaghan, Eadbhard, Oh, Sang-Yun, O'Neill, F. Anthony, Paunio, Tiina, Pietiläinen, Olli, Perkins, Diana O., Quested, Digby, Savitz, Adam, Li, Qingqin S., Schwab, Sibylle G., Shi, Jianxin, Spencer, Chris C.A., Thirumalai, Srinivas, Veijola, Juha, Waddington, John, Walsh, Dermot, Wildenauer, Dieter B., Bramon, Elvira, Darvasi, Ariel, Posthuma, Danielle, St. Clair, David, Shanta, Omar, Klein, Marieke, Park, Peter J., Weinberger, Daniel, Moran, John V., Gage, Fred H., Vaccarino, Flora M., Gleeson, Joseph, Mathern, Gary, Courchesne, Eric, Roy, Subhojit, Bizzotto, Sara, Coulter, Michael, Dias, Caroline, D'Gama, Alissa, Ganz, Javier, Hill, Robert, Huang, August Yue, Khoshkhoo, Sattar, Kim, Sonia, Lodato, Michael, Miller, Michael, Borges-Monroy, Rebeca, Rodin, Rachel, Zhou, Zinan, Bohrson, Craig, Chu, Chong, Cortes-Ciriano, Isidro, Dou, Yanmei, Galor, Alon, Gulhan, Doga, Kwon, Minseok, Luquette, Joe, Viswanadham, Vinay, Jones, Attila, Rosenbluh, Chaggai, Cho, Sean, Langmead, Ben, Thorpe, Jeremy, Erwin, Jennifer, Jaffe, Andrew, McConnell, Michael, Narurkar, Rujuta, Paquola, Apua, Shin, Jooheon, Straub, Richard, Abyzov, Alexej, Bae, Taejeong, Jang, Yeongjun, Wang, Yifan, Gage, Fred, Linker, Sara, Reed, Patrick, Wang, Meiyan, Urban, Alexander, Zhou, Bo, Zhu, Xiaowei, Pattni, Reenal, Amero, Aitor Serres, Juan, David, Lobon, Irene, Marques-Bonet, Tomas, Moruno, Manuel Solis, Perez, Raquel Garcia, Povolotskaya, Inna, Soriano, Eduardo, Averbuj, Dan, Ball, Laurel, Breuss, Martin, Yang, Xiaoxu, Chung, Changuk, Emery, Sarah B., Flasch, Diane A., Kidd, Jeffrey M., Kopera, Huira C., Kwan, Kenneth Y., Mills, Ryan E., Moldovan, John B., Sun, Chen, Zhao, Xuefang, Zhou, Weichen, Frisbie, Trenton J., Cherskov, Adriana, Fasching, Liana, Jourdon, Alexandre, Pochareddy, Sirisha, Scuderi, Soraya, Sestan, Nenad, Maury, Eduardo A., Sherman, Maxwell A., Genovese, Giulio, Gilgenast, Thomas G., Kamath, Tushar, Burris, S.J., Rajarajan, Prashanth, Flaherty, Erin, Akbarian, Schahram, Chess, Andrew, McCarroll, Steven A., Loh, Po-Ru, Phillips-Cremins, Jennifer E., Brennand, Kristen J., Macosko, Evan Z., Walters, James T.R., O’Donovan, Michael, Sullivan, Patrick, Sebat, Jonathan, Lee, Eunjung A., and Walsh, Christopher A.
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- 2023
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8. GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity
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Falk, Sarah, Petersen, Jonas, Svendsen, Charlotte, Romero-Leguizamón, Cesar R., Jørgensen, Søren Heide, Krauth, Nathalie, Ludwig, Mette Q., Lundø, Kathrine, Roostalu, Urmas, Skovbjerg, Grethe, Nielsen, Duy Anh Gurskov, Ejdrup, Aske Lykke, Pers, Tune H., Dmytriyeva, Oksana, Hecksher-Sørensen, Jacob, Gether, Ulrik, Kohlmeier, Kristi A., and Clemmensen, Christoffer
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- 2023
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9. Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia
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Ripke, Stephan, Neale, Benjamin M., Corvin, Aiden, Walters, James T.R., Farh, Kai-How, Holmans, Peter A., Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Belliveau, Richard A., Jr., Bene, Judit, Bergen, Sarah E., Bevilacqua, Elizabeth, Bigdeli, Tim B., Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa, Catts, Stanley V., Chambert, Kimberley D., Chan, Raymond C.K., Chan, Ronald Y.L., Chen, Eric Y.H., Cheng, Wei, Cheung, Eric FC., Chong, Siow Ann, Cloninger, C. Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J., Curtis, David, Davidson, Michael, Davis, Kenneth L., Degenhardt, Franziska, Del Favero, Jurgen, Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Fanous, Ayman H., Farrell, Martilias S., Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B., Friedl, Marion, Friedman, Joseph I., Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, de Haan, Lieuwe, Hammer, Christian, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Hartmann, Annette M., Henskens, Frans A., Herms, Stefan, Hirschhorn, Joel N., Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V., Hougaard, David M., Ikeda, Masashi, Joa, Inge, Julià, Antonio, Kahn, René S., Kalaydjieva, Luba, Karachanak-Yankova, Sena, Karjalainen, Juha, Kavanagh, David, Keller, Matthew C., Kennedy, James L., Khrunin, Andrey, Kim, Yunjung, Klovins, Janis, Knowles, James A., Konte, Bettina, Kucinskas, Vaidutis, Kucinskiene, Zita Ausrele, Kuzelova-Ptackova, Hana, Kähler, Anna K., Laurent, Claudine, Lee, Jimmy, Lee, S. Hong, Legge, Sophie E., Lerer, Bernard, Li, Miaoxin, Li, Tao, Liang, Kung-Yee, Lieberman, Jeffrey, Limborska, Svetlana, Loughland, Carmel M., Lubinski, Jan, Lönnqvist, Jouko, Macek, Milan, Magnusson, Patrik K.E., Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, Marsal, Sara, Mattheisen, Manuel, Mattingsdal, Morten, McCarley, Robert W., McDonald, Colm, McIntosh, Andrew M., Meier, Sandra, Meijer, Carin J., Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mokrab, Younes, Morris, Derek W., Mors, Ole, Murphy, Kieran C., Murray, Robin M., Myin-Germeys, Inez, Müller-Myhsok, Bertram, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin, Annelie, O'Callaghan, Eadbhard, O'Dushlaine, Colm, O'Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Olsen, Line, Van Os, Jim, Pantelis, Christos, Papadimitriou, George N., Papiol, Sergi, Parkhomenko, Elena, Pato, Michele T., Paunio, Tiina, Pejovic-Milovancevic, Milica, Perkins, Diana O., Pietiläinen, Olli, Pimm, Jonathan, Pocklington, Andrew J., Powell, John, Price, Alkes, Pulver, Ann E., Purcell, Shaun M., Quested, Digby, Rasmussen, Henrik B., Reichenberg, Abraham, Reimers, Mark A., Richards, Alexander L., Roffman, Joshua L., Roussos, Panos, Ruderfer, Douglas M., Salomaa, Veikko, Sanders, Alan R., Schall, Ulrich, Schubert, Christian R., Schulze, Thomas G., Schwab, Sibylle G., Scolnick, Edward M., Scott, Rodney J., Seidman, Larry J., Shi, Jianxin, Sigurdsson, Engilbert, Silagadze, Teimuraz, Silverman, Jeremy M., Sim, Kang, Slominsky, Petr, Smoller, Jordan W., So, Hon-Cheong, Spencer, Chris C.A., Stahl, Eli A., Stefansson, Hreinn, Steinberg, Stacy, Stogmann, Elisabeth, Straub, Richard E., Strengman, Eric, Strohmaier, Jana, Stroup, T Scott, Subramaniam, Mythily, Suvisaari, Jaana, Svrakic, Dragan M., Szatkiewicz, Jin P., Söderman, Erik, Thirumalai, Srinivas, Toncheva, Draga, Tosato, Sarah, Veijola, Juha, Waddington, John, Walsh, Dermot, Wang, Dai, Wang, Qiang, Webb, Bradley T., Weiser, Mark, Wildenauer, Dieter B., Williams, Nigel M., Williams, Stephanie, Witt, Stephanie H., Wolen, Aaron R., Wong, Emily H.M., Wormley, Brandon K., Xi, Hualin Simon, Zai, Clement C., Zheng, Xuebin, Zimprich, Fritz, Wray, Naomi R., Stefansson, Kari, Visscher, Peter M., Adolfsson, Rolf, Andreassen, Ole A., Blackwood, Douglas H.R., Bramon, Elvira, Buxbaum, Joseph D., Børglum, Anders D., Cichon, Sven, Darvasi, Ariel, Domenici, Enrico, Ehrenreich, Hannelore, Esko, Tõnu, Gejman, Pablo V., Gill, Michael, Gurling, Hugh, Hultman, Christina M., Iwata, Nakao, Jablensky, Assen V., Jönsson, Erik G., Kendler, Kenneth S., Kirov, George, Knight, Jo, Lencz, Todd, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., McCarroll, Steven A., McQuillin, Andrew, Moran, Jennifer L., Mortensen, Preben B., Mowry, Bryan J., Nöthen, Markus M., Ophoff, Roel A., Owen, Michael J., Palotie, Aarno, Pato, Carlos N., Petryshen, Tracey L., Posthuma, Danielle, Rietschel, Marcella, Riley, Brien P., Rujescu, Dan, Sham, Pak C., Sklar, Pamela, St Clair, David, Weinberger, Daniel R., Wendland, Jens R., Werge, Thomas, Daly, Mark J., Sullivan, Patrick F., O'Donovan, Michael C., Qin, Shengying, Sawa, Akira, Kahn, Rene, Hong, Kyung Sue, Shi, Wenzhao, Tsuang, Ming, Itokawa, Masanari, Feng, Gang, Glatt, Stephen J., Ma, Xiancang, Tang, Jinsong, Ruan, Yunfeng, Liu, Ruize, Zhu, Feng, Horiuchi, Yasue, Lee, Byung Dae, Joo, Eun-Jeong, Myung, Woojae, Ha, Kyooseob, Won, Hong-Hee, Baek, Ji Hyung, Chung, Young Chul, Kim, Sung-Wan, Kusumawardhani, Agung, Chen, Wei J., Hwu, Hai-Gwo, Hishimoto, Akitoyo, Otsuka, Ikuo, Sora, Ichiro, Toyota, Tomoko, Yoshikawa, Takeo, Kunugi, Hiroshi, Hattori, Kotaro, Ishiwata, Sayuri, Numata, Shusuke, Ohmori, Tetsuro, Arai, Makoto, Ozeki, Yuji, Fujii, Kumiko, Kim, Se Joo, Lee, Heon-Jeong, Ahn, Yong Min, Kim, Se Hyun, Akiyama, Kazufumi, Shimoda, Kazutaka, Kinoshita, Makoto, Hsu, Yu-Han H., Pintacuda, Greta, Nacu, Eugeniu, Kim, April, Tsafou, Kalliopi, Petrossian, Natalie, Crotty, William, Suh, Jung Min, Riseman, Jackson, Martin, Jacqueline M., Biagini, Julia C., Mena, Daya, Ching, Joshua K.T., Malolepsza, Edyta, Li, Taibo, Singh, Tarjinder, Ge, Tian, Egri, Shawn B., Tanenbaum, Benjamin, Stanclift, Caroline R., Apffel, Annie M., Carr, Steven A., Schenone, Monica, Jaffe, Jake, Fornelos, Nadine, Eggan, Kevin C., and Lage, Kasper
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- 2023
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10. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
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Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J., Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C., Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S., Bartz, Traci M., Bentley, Amy R., Bielak, Lawrence F., Chong, Mike, Chu, Audrey Y., Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D., Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F., Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M., Haller, Toomas, Hartwig, Fernando P., Hillis, David A., Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U., Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A., Karlsson, Robert, Kerr, Kathleen F., Kim, Boram, Koolhaas, Chantal M., Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A., Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R., Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C., Rivera, Natalia V., Robiou-du-Pont, Sebastien, Schraut, Katharina E., Schulz, Christina-Alexandra, Stringham, Heather M., Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J., Vanmunster, Mathias, van Rooij, Frank J. A., van Vliet-Ostaptchouk, Jana V., Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N., Baumeister, Sebastian E., Beilby, John, Blangero, John, Boomsma, Dorret I., Brage, Soren, Braund, Peter S., Brody, Jennifer A., Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W., Collins, Francis S., Cupples, L. Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D., Fernandez-Rhodes, Lindsay, Fohner, Alison E., Franco, Oscar H., Galesloot, Tessel E., Gordon, Scott D., Grarup, Niels, Hartman, Catharina A., Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K., Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O., Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P., Kuusisto, Johanna, Launer, Lenore J., Li, Aihua, Linneberg, Allan, Luan, Jian’an, Vidal, Pedro Marques, Medland, Sarah E., Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P., Nolte, Ilja M., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Power, Christine, Raitakari, Olli T., Reedik, Mägi, Reiner, Alex P., Ridker, Paul M., Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A., Scott, Laura J., Scott, Robert A., Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V., Smith, Jennifer A., Sonestedt, Emily, Strøm, Marin, Tai, E. Shyong, Teo, Koon K., Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G., Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L., Yuan, Jian Min, Zillikens, M. Carola, Zonderman, Alan B., Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C., Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I., Smith, George Davey, de Geus, Eco J. C., Deldicque, Louise, Dörr, Marcus, Evans, Michele K., Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Jr, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L., Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W. Craig, Kardia, Sharon L. R., Kiemeney, Lambertus A., Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K. E., Martin, Nicholas G., Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E., Ohlsson, Claes, Oldehinkel, Albertine J., Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W. J. H., Pers, Tune H., Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N., Samani, Nilesh J., Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I. A., Spector, Tim D., Timpson, Nicholas J., van Dam, Rob M., van der Velde, Nathalie, van Duijn, Cornelia M., Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J., Weir, David R., Wichmann, Heinz-Erich, Wilson, James F., Hevener, Andrea L., Krook, Anna, Zierath, Juleen R., Thomis, Martine A. I., Loos, Ruth J. F., and Hoed, Marcel den
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- 2022
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11. Hindbrain circuits in the control of eating behaviour and energy balance
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Cheng, Wenwen, Gordian, Desiree, Ludwig, Mette Q., Pers, Tune H., Seeley, Randy J., and Myers, Jr., Martin G.
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- 2022
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12. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility
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Patsopoulos, Nikolaos A, Baranzini, Sergio E, Santaniello, Adam, Shoostari, Parisa, Cotsapas, Chris, Wong, Garrett, Beecham, Ashley H, James, Tojo, Replogle, Joseph, Vlachos, Ioannis S, McCabe, Cristin, Pers, Tune H, Brandes, Aaron, White, Charles, Keenan, Brendan, Cimpean, Maria, Winn, Phoebe, Panteliadis, Ioannis-Pavlos, Robbins, Allison, Andlauer, Till FM, Zarzycki, Onigiusz, Dubois, Bénédicte, Goris, An, Søndergaard, Helle Bach, Sellebjerg, Finn, Sorensen, Per Soelberg, Ullum, Henrik, Thørner, Lise Wegner, Saarela, Janna, Cournu-Rebeix, Isabelle, Damotte, Vincent, Fontaine, Bertrand, Guillot-Noel, Lena, Lathrop, Mark, Vukusic, Sandra, Berthele, Achim, Pongratz, Viola, Buck, Dorothea, Gasperi, Christiane, Graetz, Christiane, Grummel, Verena, Hemmer, Bernhard, Hoshi, Muni, Knier, Benjamin, Korn, Thomas, Lill, Christina M, Luessi, Felix, Mühlau, Mark, Zipp, Frauke, Dardiotis, Efthimios, Agliardi, Cristina, Amoroso, Antonio, Barizzone, Nadia, Benedetti, Maria D, Bernardinelli, Luisa, Cavalla, Paola, Clarelli, Ferdinando, Comi, Giancarlo, Cusi, Daniele, Esposito, Federica, Ferrè, Laura, Galimberti, Daniela, Guaschino, Clara, Leone, Maurizio A, Martinelli, Vittorio, Moiola, Lucia, Salvetti, Marco, Sorosina, Melissa, Vecchio, Domizia, Zauli, Andrea, Santoro, Silvia, Mancini, Nicasio, Zuccalà, Miriam, Mescheriakova, Julia, van Duijn, Cornelia, Bos, Steffan D, Celius, Elisabeth G, Spurkland, Anne, Comabella, Manuel, Montalban, Xavier, Alfredsson, Lars, Bomfim, Izaura L, Gomez-Cabrero, David, Hillert, Jan, Jagodic, Maja, Lindén, Magdalena, Piehl, Fredrik, Jelčić, Ilijas, Martin, Roland, Sospedra, Mirela, Baker, Amie, Ban, Maria, Hawkins, Clive, Hysi, Pirro, Kalra, Seema, Karpe, Fredrik, Khadake, Jyoti, Lachance, Genevieve, Molyneux, Paul, and Neville, Matthew
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Neurosciences ,Brain Disorders ,Multiple Sclerosis ,Human Genome ,Autoimmune Disease ,Clinical Research ,Genetics ,Neurodegenerative ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Neurological ,Case-Control Studies ,Cell Cycle Proteins ,Chromosome Mapping ,Chromosomes ,Human ,X ,GTPase-Activating Proteins ,Gene Frequency ,Genetic Loci ,Genome-Wide Association Study ,Genomics ,Humans ,Inheritance Patterns ,Major Histocompatibility Complex ,Microglia ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,RNA-Seq ,Transcriptome ,International Multiple Sclerosis Genetics Consortium ,General Science & Technology - Abstract
We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.
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- 2019
13. Genome-wide association study identifies 30 loci associated with bipolar disorder
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Stahl, Eli A, Breen, Gerome, Forstner, Andreas J, McQuillin, Andrew, Ripke, Stephan, Trubetskoy, Vassily, Mattheisen, Manuel, Wang, Yunpeng, Coleman, Jonathan RI, Gaspar, Héléna A, de Leeuw, Christiaan A, Steinberg, Stacy, Pavlides, Jennifer M Whitehead, Trzaskowski, Maciej, Byrne, Enda M, Pers, Tune H, Holmans, Peter A, Richards, Alexander L, Abbott, Liam, Agerbo, Esben, Akil, Huda, Albani, Diego, Alliey-Rodriguez, Ney, Als, Thomas D, Anjorin, Adebayo, Antilla, Verneri, Awasthi, Swapnil, Badner, Judith A, Bækvad-Hansen, Marie, Barchas, Jack D, Bass, Nicholas, Bauer, Michael, Belliveau, Richard, Bergen, Sarah E, Pedersen, Carsten Bøcker, Bøen, Erlend, Boks, Marco P, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Bybjerg-Grauholm, Jonas, Byerley, William, Casas, Miquel, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Charney, Alexander W, Chen, Danfeng, Churchhouse, Claire, Clarke, Toni-Kim, Coryell, William, Craig, David W, Cruceanu, Cristiana, Curtis, David, Czerski, Piotr M, Dale, Anders M, de Jong, Simone, Degenhardt, Franziska, Del-Favero, Jurgen, DePaulo, J Raymond, Djurovic, Srdjan, Dobbyn, Amanda L, Dumont, Ashley, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Fan, Chun Chieh, Fischer, Sascha B, Flickinger, Matthew, Foroud, Tatiana M, Forty, Liz, Frank, Josef, Fraser, Christine, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartolomei, Claudia, Pedersen, Marianne Giørtz, Goldstein, Jaqueline, Gordon, Scott D, Gordon-Smith, Katherine, Green, Elaine K, Green, Melissa J, Greenwood, Tiffany A, Grove, Jakob, Guan, Weihua, Guzman-Parra, José, Hamshere, Marian L, Hautzinger, Martin, Heilbronner, Urs, Herms, Stefan, Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, and Juréus, Anders
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Biological Sciences ,Genetics ,Serious Mental Illness ,Mental Health ,Human Genome ,Brain Disorders ,Schizophrenia ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Bipolar Disorder ,Case-Control Studies ,Depressive Disorder ,Major ,Female ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Male ,Polymorphism ,Single Nucleotide ,Psychotic Disorders ,Systems Biology ,eQTLGen Consortium ,BIOS Consortium ,Bipolar Disorder Working Group of the Psychiatric Genomics Consortium ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P
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- 2019
14. Population‐based identity‐by‐descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia
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Harold, Denise, Connolly, Siobhan, Riley, Brien P, Kendler, Kenneth S, McCarthy, Shane E, McCombie, William R, Richards, Alex, Owen, Michael J, O'Donovan, Michael C, Walters, James, Donnelly, Peter, Bates, Lesley, Barroso, Ines, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin NA, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas W, Spencer, Chris CA, Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Giannoulatou, Eleni, Hopkins, Lucinda, Pirinen, Matti, Pearson, Richard, Strange, Amy, Su, Zhan, Vukcevic, Damjan, Langford, Cordelia, Hunt, Sarah E, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T, Liddle, Jennifer, Potter, Simon C, Ravindrarajah, Radhi, Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Ripke, Stephan, Neale, Benjamin M, Walters, James TR, Farh, Kai‐How, Holmans, Peter A, Lee, Phil, Bulik‐Sullivan, Brendan, Collier, David A, Huang, Hailiang, Pers, Tune H, Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A, Begemann, Martin, Belliveau, Richard A, Bene, Judit, Bergen, Sarah E, Bevilacqua, Elizabeth, Bigdeli, Tim B, Black, Donald W, Bruggeman, Richard, Buccola, Nancy G, Buckner, Randy L, Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M, Carr, Vaughan J, Carrera, Noa, Catts, Stanley V, Chambert, Kimberley D, Chan, Raymond CK, and Chan, Ronald YL
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Biological Sciences ,Genetics ,Clinical Research ,Schizophrenia ,Brain Disorders ,Human Genome ,Prevention ,Serious Mental Illness ,Mental Health ,Aetiology ,2.1 Biological and endogenous factors ,Adult ,Case-Control Studies ,Chromosome Mapping ,DNA Copy Number Variations ,Databases ,Genetic ,Exome ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Haplotypes ,Humans ,Male ,Middle Aged ,Risk Factors ,Sequence Analysis ,DNA ,Exome Sequencing ,GWAS ,IBD mapping ,rare variants ,Wellcome Trust Case Control Consortium 2 ,Schizophrenia Working Group of the Psychiatric Genomics Consortium ,Clinical Sciences ,Neurosciences ,Clinical sciences - Abstract
Genome-wide association studies (GWASs) are highly effective at identifying common risk variants for schizophrenia. Rare risk variants are also important contributors to schizophrenia etiology but, with the exception of large copy number variants, are difficult to detect with GWAS. Exome and genome sequencing, which have accelerated the study of rare variants, are expensive so alternative methods are needed to aid detection of rare variants. Here we re-analyze an Irish schizophrenia GWAS dataset (n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.
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- 2019
15. A single-cell atlas of human and mouse white adipose tissue
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Emont, Margo P., Jacobs, Christopher, Essene, Adam L., Pant, Deepti, Tenen, Danielle, Colleluori, Georgia, Di Vincenzo, Angelica, Jørgensen, Anja M., Dashti, Hesam, Stefek, Adam, McGonagle, Elizabeth, Strobel, Sophie, Laber, Samantha, Agrawal, Saaket, Westcott, Gregory P., Kar, Amrita, Veregge, Molly L., Gulko, Anton, Srinivasan, Harini, Kramer, Zachary, De Filippis, Eleanna, Merkel, Erin, Ducie, Jennifer, Boyd, Christopher G., Gourash, William, Courcoulas, Anita, Lin, Samuel J., Lee, Bernard T., Morris, Donald, Tobias, Adam, Khera, Amit V., Claussnitzer, Melina, Pers, Tune H., Giordano, Antonio, Ashenberg, Orr, Regev, Aviv, Tsai, Linus T., and Rosen, Evan D.
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- 2022
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16. Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis
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Fred, Rikard G., Steen Pedersen, Julie, Thompson, Jonatan J., Lee, Julie, Timshel, Pascal N., Stender, Stefan, Opseth Rygg, Marte, Gluud, Lise Lotte, Bjerregaard Kristiansen, Viggo, Bendtsen, Flemming, Hansen, Torben, and Pers, Tune H.
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- 2022
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17. Author Correction: A single-cell atlas of human and mouse white adipose tissue
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Emont, Margo P., Jacobs, Christopher, Essene, Adam L., Pant, Deepti, Tenen, Danielle, Colleluori, Georgia, Di Vincenzo, Angelica, Jørgensen, Anja M., Dashti, Hesam, Stefek, Adam, McGonagle, Elizabeth, Strobel, Sophie, Laber, Samantha, Agrawal, Saaket, Westcott, Gregory P., Kar, Amrita, Veregge, Molly L., Gulko, Anton, Srinivasan, Harini, Kramer, Zachary, De Filippis, Eleanna, Merkel, Erin, Ducie, Jennifer, Boyd, Christopher G., Gourash, William, Courcoulas, Anita, Lin, Samuel J., Lee, Bernard T., Morris, Donald, Tobias, Adam, Khera, Amit V., Claussnitzer, Melina, Pers, Tune H., Giordano, Antonio, Ashenberg, Orr, Regev, Aviv, Tsai, Linus T., and Rosen, Evan D.
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- 2023
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18. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity
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Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J.E., Veldink, Jan H., Ruigrok, Ynte M., Hege Aamodt, Anne, Heidi Skogholt, Anne, Brumpton, Ben M, Willer, Cristen J, Sandset, Else C, Kristoffersen, Espen S, Ellekjær, Hanne, Heuch, Ingrid, Nielsen, Jonas B, Hagen, Knut, Hveem, Kristian, Fritsche, Lars G, Thomas, Laurent F, Pedersen, Linda M, Gabrielsen, Maiken E, Holmen, Oddgeir L, Børte, Sigrid, Zhou, Wei, Abboud, Shérine, Pandolfo, Massimo, Thijs, Vincent, Leys, Didier, Bodenant, Marie, Louillet, Fabien, Touzé, Emmanuel, Mas, Jean-Louis, Samson, Yves, Leder, Sara, Léger, Anne, Deltour, Sandrine, Crozier, Sophie, Méresse, Isabelle, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Béjot, Yannick, Decavel, Pierre, Medeiros, Elizabeth, Montiel, Paola, Moulin, Thierry, Vuillier, Fabrice, Dallongeville, Jean, Metso, Antti J, Metso, Tiina, Tatlisumak, Turgut, Grond-Ginsbach, Caspar, Lichy, Christoph, Kloss, Manja, Werner, Inge, Arnold, Marie-Luise, Dos Santos, Michael, Grau, Armin, Dichgans, Martin, Thomas-Feles, Constanze, Weber, Ralf, Brandt, Tobias, Pezzini, Alessandro, De Giuli, Valeria, Caria, Filomena, Poli, Loris, Padovani, Alessandro, Bersano, Anna, Lanfranconi, Silvia, Beretta, Simone, Ferrarese, Carlo, Giacolone, Giacomo, Paolucci, Stefano, Lyrer, Philippe, Engelter, Stefan, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Bonati, Leo, Gensicke, Henrik, Amort, Margareth, Markus, Hugh, Majersik, Jennifer, Worrall, Bradford, Southerland, Andrew, Cole, John, Kittner, Steven, Evangelou, Evangelos, Warren, Helen R, Gao, He, Ntritsos, Georgios, Dimou, Niki, Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G, Jackson, Anne U, Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian’an, Mangino, Massimo, Oldmeadow, Christopher, Peter Prins, Bram, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M, Zhao, Jing-Hua, Connell, John, de Mutsert, Renée, Doney, Alex SF, Farrall, Martin, Menni, Cristina, Morris, Andrew D, Noordam, Raymond, Paré, Guillaume, Poulter, Neil R, Shields, Denis C, Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E, Ayers, Kristin L, Barbieri, Caterina M, Batini, Chiara, Bis, Joshua C, Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I, Bottinger, Erwin P, Braund, Peter S, Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J, Davies, Gail, de Borst, Martin H, de Geus, Eco J, Deary, Ian J, Deelen, Joris, Del Greco M, Fabiola, Yusuf Demirkale, Cumhur, Dörr, Marcus, Ehret, Georg B, Elosua, Roberto, Enroth, Stefan, Mesut Erzurumluoglu, A, Ferreira, Teresa, Frånberg, Mattias, Franco, Oscar H, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan J, Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B, Harris, Sarah E, Hartman, Catharina A, Havulinna, Aki S, Hicks, Andrew A, Hofer, Edith, Hofman, Albert, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Åsa, Johnson, Andrew D, Joshi, Peter K, Jousilahti, Pekka, Wouter Jukema, J, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D, Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S, Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J, Lehne, Benjamin, Lehtimäki, Terho, Liewald, David CM, Lin, Li, Lind, Lars, Lindgren, Cecilia M, Liu, YongMei, Loos, Ruth JF, Lopez, Lorna M, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew P, Morrison, Alanna C, Munson, Peter J, Nalls, Mike A, Nandakumar, Priyanka, Nelson, Christopher P, Niiranen, Teemu, Nolte, Ilja M, Nutile, Teresa, Oldehinkel, Albertine J, Oostra, Ben A, O’Reilly, Paul F, Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, WJH Penninx, Brenda, Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P, Tri Nguyen, Quang, Raitakari, Olli T, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M, Ried, Janina S, Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M, Rotter, Jerome I, Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F, Salomaa, Veikko, Samani, Nilesh J, Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V, Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M, Stott, David J, Strachan, David P, Strawbridge, Rona J, Sundström, Johan, Swertz, Morris A, Taylor, Kent D, Teumer, Alexander, Tobin, Martin D, Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaakko, Tzourio, Christophe, Uitterlinden, André G, Vaez, Ahmad, van der Most, Peter J, van Duijn, Cornelia M, Verwoert, Germaine C, Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Wilson, James F, Wright, Alan F, Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R, Butterworth, Adam S, Chasman, Daniel I, Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna MM, Laakso, Markku, Lakatta, Edward G, Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O, Palmer, Colin NA, Risch, Lorenz, Scott, Robert A, Scott, Rodney J, Sever, Peter, Spector, Tim D, van der Harst, Pim, Wareham, Nicholas J, Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B, Newton-Cheh, Christopher, Brown, Morris J, Metspalu, Andres, Psaty, Bruce M., Wain, Louise V, Elliott, Paul, Caulfield, Mark J, Gormley, Padhraig, Anttila, Verneri, Palta, Priit, Esko, Tonu, Pers, Tune H, Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A, Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M, Kallela, Mikko, Freilinger, Tobias M, Ran, Caroline, Gordon, Scott G, Stam, Anine H, Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H H, Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A, Buring, Julie E, Schürks, Markus, Ridker, Paul M, Gudlaug Hrafnsdottir, Maria, Stefansson, Hreinn, Ring, Susan M, Hottenga, Jouke-Jan, Penninx, Brenda W J H, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C, Madden, Pamela A F, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E, Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H, Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G, Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G, Hofman, Albert, van Duijn, Cornelia M, Cherkas, Lynn, Pedersen, Linda M, Stubhaug, Audun, Nielsen, Christopher S, Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Francke Christensen, Anne, Folkmann Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J, Raitakari, Olli, Arfan Ikram, M, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P, Ferrari, Michel D, Belin, Andrea C, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M J M, Boomsma, Dorret I, Davey Smith, George, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J, Neale, Benjamin M, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Palotie, Aarno, Akiyama, Masato, Alg, Varinder S., Børte, Sigrid, Broderick, Joseph P., Brumpton, Ben M., Dauvillier, Jérôme, Desal, Hubert, Dina, Christian, Friedrich, Christoph M., Gaál-Paavola, Emília I., Gentric, Jean-Christophe, Hirsch, Sven, Hostettler, Isabel C., Houlden, Henry, Hveem, Kristian, Jääskeläinen, Juha E., Johnsen, Marianne Bakke, Li, Liming, Lin, Kuang, Lindgren, Antti, Martin, Olivier, Matsuda, Koichi, Millwood, Iona Y., Naggara, Olivier, Niemelä, Mika, Pera, Joanna, Redon, Richard, Rouleau, Guy A., Sandvei, Marie Søfteland, Schilling, Sabine, Shotar, Eimad, Slowik, Agnieszka, Terao, Chikashi, Verschuren, W. M. Monique, Walters, Robin G., Werring, David J., Willer, Cristen J., Woo, Daniel, Worrall, Bradford B., and Zhou, Sirui
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- 2023
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19. Genetic analysis of dietary intake identifies new loci and functional links with metabolic traits
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Merino, Jordi, Dashti, Hassan S., Sarnowski, Chloé, Lane, Jacqueline M., Todorov, Petar V., Udler, Miriam S., Song, Yanwei, Wang, Heming, Kim, Jaegil, Tucker, Chandler, Campbell, John, Tanaka, Toshiko, Chu, Audrey Y., Tsai, Linus, Pers, Tune H., Chasman, Daniel I., Rutter, Martin K., Dupuis, Josée, Florez, Jose C., and Saxena, Richa
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- 2022
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20. Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour
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Mills, Melinda C., Tropf, Felix C., Brazel, David M., van Zuydam, Natalie, Vaez, Ahmad, Pers, Tune H., Snieder, Harold, Perry, John R. B., Ong, Ken K., den Hoed, Marcel, Barban, Nicola, and Day, Felix R.
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- 2021
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21. Protocol for flow cytometry-assisted single-nucleus RNA sequencing of human and mouse adipose tissue with sample multiplexing
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Gulko, Anton, primary, Essene, Adam, additional, Belmont-Rausch, Dylan Matthew, additional, Veregge, Molly, additional, Pant, Deepti, additional, Tenen, Danielle, additional, Kapel, Benedicte Schultz, additional, Emont, Margo P., additional, Pers, Tune H., additional, Rosen, Evan D., additional, and Tsai, Linus T., additional
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- 2024
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22. Role of hypothalamic MAPK/ERK signaling and central action of FGF1 in diabetes remission
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Brown, Jenny M., Bentsen, Marie A., Rausch, Dylan M., Phan, Bao Anh, Wieck, Danielle, Wasanwala, Huzaifa, Matsen, Miles E., Acharya, Nikhil, Richardson, Nicole E., Zhao, Xin, Zhai, Peng, Secher, Anna, Morton, Gregory J., Pers, Tune H., Schwartz, Michael W., and Scarlett, Jarrad M.
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- 2021
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23. An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
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Scott, Robert A, Scott, Laura J, Mägi, Reedik, Marullo, Letizia, Gaulton, Kyle J, Kaakinen, Marika, Pervjakova, Natalia, Pers, Tune H, Johnson, Andrew D, Eicher, John D, Jackson, Anne U, Ferreira, Teresa, Lee, Yeji, Ma, Clement, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Qi, Lu, Van Zuydam, Natalie R, Mahajan, Anubha, Chen, Han, Almgren, Peter, Voight, Ben F, Grallert, Harald, Müller-Nurasyid, Martina, Ried, Janina S, Rayner, William N, Robertson, Neil, Karssen, Lennart C, van Leeuwen, Elisabeth M, Willems, Sara M, Fuchsberger, Christian, Kwan, Phoenix, Teslovich, Tanya M, Chanda, Pritam, Li, Man, Lu, Yingchang, Dina, Christian, Thuillier, Dorothee, Yengo, Loic, Jiang, Longda, Sparso, Thomas, Kestler, Hans A, Chheda, Himanshu, Eisele, Lewin, Gustafsson, Stefan, Frånberg, Mattias, Strawbridge, Rona J, Benediktsson, Rafn, Hreidarsson, Astradur B, Kong, Augustine, Sigurðsson, Gunnar, Kerrison, Nicola D, Luan, Jian'an, Liang, Liming, Meitinger, Thomas, Roden, Michael, Thorand, Barbara, Esko, Tõnu, Mihailov, Evelin, Fox, Caroline, Liu, Ching-Ti, Rybin, Denis, Isomaa, Bo, Lyssenko, Valeriya, Tuomi, Tiinamaija, Couper, David J, Pankow, James S, Grarup, Niels, Have, Christian T, Jørgensen, Marit E, Jørgensen, Torben, Linneberg, Allan, Cornelis, Marilyn C, van Dam, Rob M, Hunter, David J, Kraft, Peter, Sun, Qi, Edkins, Sarah, Owen, Katharine R, Perry, John RB, Wood, Andrew R, Zeggini, Eleftheria, Tajes-Fernandes, Juan, Abecasis, Goncalo R, Bonnycastle, Lori L, Chines, Peter S, Stringham, Heather M, Koistinen, Heikki A, Kinnunen, Leena, Sennblad, Bengt, Mühleisen, Thomas W, Nöthen, Markus M, Pechlivanis, Sonali, Baldassarre, Damiano, Gertow, Karl, Humphries, Steve E, Tremoli, Elena, Klopp, Norman, Meyer, Julia, and Steinbach, Gerald
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Human Genome ,Diabetes ,Obesity ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Metabolic and endocrine ,Diabetes Mellitus ,Type 2 ,Gene Expression Regulation ,Genetic Variation ,Genome-Wide Association Study ,Humans ,White People ,DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium ,Medical and Health Sciences ,Endocrinology & Metabolism - Abstract
To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 × 10-8), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
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- 2017
24. A Low-Frequency Inactivating Akt2 Variant Enriched in the Finnish Population is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk.
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Manning, Alisa, Highland, Heather M, Gasser, Jessica, Sim, Xueling, Tukiainen, Taru, Fontanillas, Pierre, Grarup, Niels, Rivas, Manuel A, Mahajan, Anubha, Locke, Adam E, Cingolani, Pablo, Pers, Tune H, Viñuela, Ana, Brown, Andrew A, Wu, Ying, Flannick, Jason, Fuchsberger, Christian, Gamazon, Eric R, Gaulton, Kyle J, Im, Hae Kyung, Teslovich, Tanya M, Blackwell, Thomas W, Bork-Jensen, Jette, Burtt, Noël P, Chen, Yuhui, Green, Todd, Hartl, Christopher, Kang, Hyun Min, Kumar, Ashish, Ladenvall, Claes, Ma, Clement, Moutsianas, Loukas, Pearson, Richard D, Perry, John RB, Rayner, N William, Robertson, Neil R, Scott, Laura J, van de Bunt, Martijn, Eriksson, Johan G, Jula, Antti, Koskinen, Seppo, Lehtimäki, Terho, Palotie, Aarno, Raitakari, Olli T, Jacobs, Suzanne BR, Wessel, Jennifer, Chu, Audrey Y, Scott, Robert A, Goodarzi, Mark O, Blancher, Christine, Buck, Gemma, Buck, David, Chines, Peter S, Gabriel, Stacey, Gjesing, Anette P, Groves, Christopher J, Hollensted, Mette, Huyghe, Jeroen R, Jackson, Anne U, Jun, Goo, Justesen, Johanne Marie, Mangino, Massimo, Murphy, Jacquelyn, Neville, Matt, Onofrio, Robert, Small, Kerrin S, Stringham, Heather M, Trakalo, Joseph, Banks, Eric, Carey, Jason, Carneiro, Mauricio O, DePristo, Mark, Farjoun, Yossi, Fennell, Timothy, Goldstein, Jacqueline I, Grant, George, Hrabé de Angelis, Martin, Maguire, Jared, Neale, Benjamin M, Poplin, Ryan, Purcell, Shaun, Schwarzmayr, Thomas, Shakir, Khalid, Smith, Joshua D, Strom, Tim M, Wieland, Thomas, Lindstrom, Jaana, Brandslund, Ivan, Christensen, Cramer, Surdulescu, Gabriela L, Lakka, Timo A, Doney, Alex SF, Nilsson, Peter, Wareham, Nicholas J, Langenberg, Claudia, Varga, Tibor V, Franks, Paul W, Rolandsson, Olov, Rosengren, Anders H, and Farook, Vidya S
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Genetics ,Diabetes ,Aetiology ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Black or African American ,Alleles ,Asian People ,Case-Control Studies ,Diabetes Mellitus ,Type 2 ,Fasting ,Finland ,Gene Frequency ,Genetic Predisposition to Disease ,Genotype ,Hispanic or Latino ,Humans ,Insulin ,Insulin Resistance ,Odds Ratio ,Proto-Oncogene Proteins c-akt ,White People ,Medical and Health Sciences ,Endocrinology & Metabolism - Abstract
To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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- 2017
25. Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function
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Wild, Philipp S, Felix, Janine F, Schillert, Arne, Teumer, Alexander, Chen, Ming-Huei, Leening, Maarten JG, Völker, Uwe, Großmann, Vera, Brody, Jennifer A, Irvin, Marguerite R, Shah, Sanjiv J, Pramana, Setia, Lieb, Wolfgang, Schmidt, Reinhold, Stanton, Alice V, Malzahn, Dörthe, Smith, Albert Vernon, Sundström, Johan, Minelli, Cosetta, Ruggiero, Daniela, Lyytikäinen, Leo-Pekka, Tiller, Daniel, Smith, J Gustav, Monnereau, Claire, Di Tullio, Marco R, Musani, Solomon K, Morrison, Alanna C, Pers, Tune H, Morley, Michael, Kleber, Marcus E, Aragam, Jayashri, Benjamin, Emelia J, Bis, Joshua C, Bisping, Egbert, Broeckel, Ulrich, Cheng, Susan, Deckers, Jaap W, Del Greco M, Fabiola, Edelmann, Frank, Fornage, Myriam, Franke, Lude, Friedrich, Nele, Harris, Tamara B, Hofer, Edith, Hofman, Albert, Huang, Jie, Hughes, Alun D, Kähönen, Mika, investigators, KNHI, Kruppa, Jochen, Lackner, Karl J, Lannfelt, Lars, Laskowski, Rafael, Launer, Lenore J, Leosdottir, Margrét, Lin, Honghuang, Lindgren, Cecilia M, Loley, Christina, MacRae, Calum A, Mascalzoni, Deborah, Mayet, Jamil, Medenwald, Daniel, Morris, Andrew P, Müller, Christian, Müller-Nurasyid, Martina, Nappo, Stefania, Nilsson, Peter M, Nuding, Sebastian, Nutile, Teresa, Peters, Annette, Pfeufer, Arne, Pietzner, Diana, Pramstaller, Peter P, Raitakari, Olli T, Rice, Kenneth M, Rivadeneira, Fernando, Rotter, Jerome I, Ruohonen, Saku T, Sacco, Ralph L, Samdarshi, Tandaw E, Schmidt, Helena, Sharp, Andrew SP, Shields, Denis C, Sorice, Rossella, Sotoodehnia, Nona, Stricker, Bruno H, Surendran, Praveen, Thom, Simon, Töglhofer, Anna M, Uitterlinden, André G, Wachter, Rolf, Völzke, Henry, Ziegler, Andreas, Münzel, Thomas, März, Winfried, Cappola, Thomas P, Hirschhorn, Joel N, Mitchell, Gary F, Smith, Nicholas L, and Fox, Ervin R
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Human Genome ,Clinical Research ,Prevention ,Heart Disease ,Cardiovascular ,2.1 Biological and endogenous factors ,Aetiology ,Female ,Genetic Loci ,Genome-Wide Association Study ,Heart Diseases ,Humans ,Male ,Myocardium ,Polymorphism ,Single Nucleotide ,Quantitative Trait ,Heritable ,Medical and Health Sciences ,Immunology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundUnderstanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function.MethodsA GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function.ResultsThe discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue.ConclusionThe additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.FundingFor detailed information per study, see Acknowledgments.
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- 2017
26. Protocol for flow cytometry-assisted single-nucleus RNA sequencing of human and mouse adipose tissue with sample multiplexing
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Gulko, Anton, Essene, Adam, Belmont-rausch, Dylan Matthew, Veregge, Molly, Pant, Deepti, Tenen, Danielle, Kapel, Benedicte Schultz, Emont, Margo P., Pers, Tune H., Rosen, Evan D., Tsai, Linus T., Gulko, Anton, Essene, Adam, Belmont-rausch, Dylan Matthew, Veregge, Molly, Pant, Deepti, Tenen, Danielle, Kapel, Benedicte Schultz, Emont, Margo P., Pers, Tune H., Rosen, Evan D., and Tsai, Linus T.
- Abstract
Adipocyte size and fragility and commercial kit costs impose significant limitations on single-cell RNA sequencing of adipose tissue. Accordingly, we developed a workflow to isolate and sample-barcode nuclei from individual adipose tissue samples, integrating flow cytometry for quality control, counting, and precise nuclei pooling for direct loading onto the popular 103 Chromium controller. This approach can eliminate batch confounding, and significantly reduces poorquality nuclei, ambient RNA contamination, and droplet loading-associated reagent waste, resulting in pronounced improvements in information content and cost efficiency.
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- 2024
27. A genetic map of the mouse dorsal vagal complex and its role in obesity
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Ludwig, Mette Q., Cheng, Wenwen, Gordian, Desiree, Lee, Julie, Paulsen, Sarah J., Hansen, Stine N., Egerod, Kristoffer L., Barkholt, Pernille, Rhodes, Christopher J., Secher, Anna, Knudsen, Lotte Bjerre, Pyke, Charles, Myers, Jr, Martin G., and Pers, Tune H.
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- 2021
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28. The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls
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Byrne, Enda M., Forstner, Andreas J., Holmans, Peter A., de Leeuw, Christiaan A., Mattheisen, Manuel, McQuillin, Andrew, Whitehead Pavlides, Jennifer M., Pers, Tune H., Ripke, Stephan, Stahl, Eli A., Steinberg, Stacy, Trubetskoy, Vassily, Trzaskowski, Maciej, Wang, Yunpeng, Abbott, Liam, Abdellaoui, Abdel, Adams, Mark J., Adolfsson, Annelie Nordin, Agerbo, Esben, Akil, Huda, Albani, Diego, Alliey-Rodriguez, Ney, Als, Thomas D., Andlauer, Till F.M., Anjorin, Adebayo, Antilla, Verneri, Van der Auwera, Sandra, Awasthi, Swapnil, Bacanu, Silviu-Alin, Badner, Judith A., Bækvad-Hansen, Marie, Barchas, Jack D., Bass, Nicholas, Bauer, Michael, Beekman, Aartjan T.F., Belliveau, Richard, Bergen, Sarah E., Bigdeli, Tim B., Binder, Elisabeth B., Bøen, Erlend, Boks, Marco, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Byerley, William, Cai, Na, Casas, Miquel, Castelao, Enrique, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Charney, Alexander W., Chen, Danfeng, Christensen, Jane Hvarregaard, Churchhouse, Claire, St Clair, David, Clarke, Toni-Kim, Colodro-Conde, Lucía, Coryell, William, Couvy-Duchesne, Baptiste, Craig, David W., Crawford, Gregory E., Cruceanu, Cristiana, Czerski, Piotr M., Dale, Anders M., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Del-Favero, Jurgen, DePaulo, J Raymond, Derks, Eske M., Direk, Nese, Djurovic, Srdjan, Dobbyn, Amanda L., Dolan, Conor V., Dumont, Ashley, Dunn, Erin C., Eley, Thalia C., Elvsåshagen, Torbjørn, Escott-Price, Valentina, Fan, Chun Chieh, Finucane, Hilary K., Fischer, Sascha B., Flickinger, Matthew, Foo, Jerome C., Foroud, Tatiana M., Forty, Liz, Frank, Josef, Fraser, Christine, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartolomei, Claudia, Goes, Fernando S., Goldstein, Jaqueline, Gordon, Scott D., Gordon-Smith, Katherine, Green, Elaine K., Green, Melissa J., Greenwood, Tiffany A., Grove, Jakob, Guan, Weihua, Hall, Lynsey S., Hamshere, Marian L., Hansen, Christine Søholm, Hansen, Thomas F., Hautzinger, Martin, Heilbronner, Urs, van Hemert, Albert M., Herms, Stefan, Hickie, Ian B., Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Huckins, Laura, Ising, Marcus, Jamain, Stéphane, Jansen, Rick, Johnson, Jessica S., de Jong, Simone, Jorgenson, Eric, Juréus, Anders, Kandaswamy, Radhika, Karlsson, Robert, Kennedy, James L., Hassan Kiadeh, Farnush Farhadi, Kittel-Schneider, Sarah, Knowles, James A., Kogevinas, Manolis, Kohane, Isaac S., Koller, Anna C., Kraft, Julia, Kretzschmar, Warren W., Krogh, Jesper, Kupka, Ralph, Kutalik, Zoltán, Lavebratt, Catharina, Lawrence, Jacob, Lawson, William B., Leber, Markus, Lee, Phil H., Levy, Shawn E., Li, Jun Z., Li, Yihan, Lind, Penelope A., Liu, Chunyu, Olde Loohuis, Loes M., Maaser, Anna, MacIntyre, Donald J., MacKinnon, Dean F., Mahon, Pamela B., Maier, Wolfgang, Maier, Robert M., Marchini, Jonathan, Martinsson, Lina, Mbarek, Hamdi, McCarroll, Steve, McGrath, Patrick, McGuffin, Peter, McInnis, Melvin G., McKay, James D., Medeiros, Helena, Medland, Sarah E., Mehta, Divya, Meng, Fan, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mirza, Saira Saeed, Mondimore, Francis M., Montgomery, Grant W., Morris, Derek W., Mostafavi, Sara, Mühleisen, Thomas W., Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nguyen, Hoang, Nievergelt, Caroline M., Nivard, Michel G., Nwulia, Evaristus A., Nyholt, Dale R., O'Donovan, Claire, O'Reilly, Paul F., Ori, Anil P.S., Oruc, Lilijana, Ösby, Urban, Oskarsson, Hogni, Painter, Jodie N., Parra, José Guzman, Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Perry, Amy, Peterson, Roseann E., Pettersson, Erik, Peyrot, Wouter J., Pfennig, Andrea, Pistis, Giorgio, Purcell, Shaun M., Quiroz, Jorge A., Qvist, Per, Regeer, Eline J., Reif, Andreas, Reinbold, Céline S., Rice, John P., Riley, Brien P., Rivas, Fabio, Rivera, Margarita, Roussos, Panos, Ruderfer, Douglas M., Ryu, Euijung, Sánchez-Mora, Cristina, Schatzberg, Alan F., Scheftner, William A., Schoevers, Robert, Schork, Nicholas J., Schulte, Eva C., Shehktman, Tatyana, Shen, Ling, Shi, Jianxin, Shilling, Paul D., Shyn, Stanley I., Sigurdsson, Engilbert, Slaney, Claire, Smeland, Olav B., Smit, Johannes H., Smith, Daniel J., Sobell, Janet L., Spijker, Anne T., Steffens, Michael, Strauss, John S., Streit, Fabian, Strohmaier, Jana, Szelinger, Szabolcs, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Robert C., Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Uitterlinden, André G., Umbricht, Daniel, Vedder, Helmut, Viktorin, Alexander, Visscher, Peter M., Wang, Weiqing, Watson, Stanley J., Webb, Bradley T., Weickert, Cynthia Shannon, Weickert, Thomas W., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Xu, Wei, Yang, Jian, Young, Allan H., Zandi, Peter, Zhang, Peng, Zhang, Futao, Zollner, Sebastian, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Arolt, Volker, Backlund, Lena, Baune, Bernhard T., Bellivier, Frank, Berger, Klaus, Berrettini, Wade H., Biernacka, Joanna M., Blackwood, Douglas H.R., Boehnke, Michael, Boomsma, Dorret I., Corvin, Aiden, Craddock, Nicholas, Daly, Mark J., Dannlowski, Udo, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Etain, Bruno, Frye, Mark, Fullerton, Janice M., Gershon, Elliot S., de Geus, E.J.C., Gill, Michael, Goes, Fernando, Grabe, Hans J., Grigoroiu-Serbanescu, Maria, Hamilton, Steven P., Hauser, Joanna, Hayward, Caroline, Heath, Andrew C., Hougaard, David M., Hultman, Christina M., Jones, Ian, Jones, Lisa A., Kahn, René S., Kendler, Kenneth S., Kirov, George, Kloiber, Stefan, Landén, Mikael, Leboyer, Marion, Lewis, Glyn, Li, Qingqin S., Lissowska, Jolanta, Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., Mayoral, Fermin, McElroy, Susan L., McIntosh, Andrew M., McMahon, Francis J., Melle, Ingrid, Metspalu, Andres, Mitchell, Philip B., Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Myers, Richard M., Neale, Benjamin M., Nimgaonkar, Vishwajit, Nordentoft, Merete, Nöthen, Markus M., O'Donovan, Michael C., Oedegaard, Ketil J., Owen, Michael J., Paciga, Sara A., Pato, Carlos, Pato, Michele T., Pedersen, Nancy L., Penninx, Brenda W.J. H., Perlis, Roy H., Porteous, David J., Posthuma, Danielle, Potash, James B., Preisig, Martin, Ramos-Quiroga, Josep Antoni, Ribasés, Marta, Rietschel, Marcella, Rouleau, Guy A., Schaefer, Catherine, Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Serretti, Alessandro, Smoller, Jordan W., Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Tiemeier, Henning, Turecki, Gustavo, Uher, Rudolf, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Andreassen, Ole A., Børglum, Anders D., Cichon, Sven, Edenberg, Howard J., Di Florio, Arianna, Kelsoe, John, Levinson, Douglas F., Lewis, Cathryn M., Nurnberger, John I., Ophoff, Roel A., Scott, Laura J., Sklar, Pamela, Sullivan, Patrick F., Wray, Naomi R., Coleman, Jonathan R.I., Gaspar, Héléna A., Bryois, Julien, and Breen, Gerome
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- 2020
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29. Protection against overfeeding-induced weight gain is preserved in obesity but does not require FGF21 or MC4R
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Lund, Camilla, primary, Ranea-Robles, Pablo, additional, Falk, Sarah, additional, Rausch, Dylan M., additional, Skovbjerg, Grethe, additional, Vibe-Petersen, Victoria Kamma, additional, Krauth, Nathalie, additional, Skytte, Jacob Lercke, additional, Vana, Vasiliki, additional, Roostalu, Urmas, additional, Pers, Tune H., additional, Lund, Jens, additional, and Clemmensen, Christoffer, additional
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- 2024
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- View/download PDF
30. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.
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Ehret, Georg B, Ferreira, Teresa, Chasman, Daniel I, Jackson, Anne U, Schmidt, Ellen M, Johnson, Toby, Thorleifsson, Gudmar, Luan, Jian'an, Donnelly, Lousie A, Kanoni, Stavroula, Petersen, Ann-Kristin, Pihur, Vasyl, Strawbridge, Rona J, Shungin, Dmitry, Hughes, Maria F, Meirelles, Osorio, Kaakinen, Marika, Bouatia-Naji, Nabila, Kristiansson, Kati, Shah, Sonia, Kleber, Marcus E, Guo, Xiuqing, Lyytikäinen, Leo-Pekka, Fava, Cristiano, Eriksson, Niclas, Nolte, Ilja M, Magnusson, Patrik K, Salfati, Elias L, Rallidis, Loukianos S, Theusch, Elizabeth, Smith, Andrew JP, Folkersen, Lasse, Witkowska, Kate, Pers, Tune H, Joehanes, Roby, Kim, Stuart K, Lataniotis, Lazaros, Jansen, Rick, Johnson, Andrew D, Warren, Helen, Kim, Young Jin, Zhao, Wei, Wu, Ying, Tayo, Bamidele O, Bochud, Murielle, CHARGE-EchoGen consortium, CHARGE-HF consortium, Wellcome Trust Case Control Consortium, Absher, Devin, Adair, Linda S, Amin, Najaf, Arking, Dan E, Axelsson, Tomas, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Barnes, Michael R, Barroso, Inês, Bevan, Stephen, Bis, Joshua C, Bjornsdottir, Gyda, Boehnke, Michael, Boerwinkle, Eric, Bonnycastle, Lori L, Boomsma, Dorret I, Bornstein, Stefan R, Brown, Morris J, Burnier, Michel, Cabrera, Claudia P, Chambers, John C, Chang, I-Shou, Cheng, Ching-Yu, Chines, Peter S, Chung, Ren-Hua, Collins, Francis S, Connell, John M, Döring, Angela, Dallongeville, Jean, Danesh, John, de Faire, Ulf, Delgado, Graciela, Dominiczak, Anna F, Doney, Alex SF, Drenos, Fotios, Edkins, Sarah, Eicher, John D, Elosua, Roberto, Enroth, Stefan, Erdmann, Jeanette, Eriksson, Per, Esko, Tonu, Evangelou, Evangelos, Evans, Alun, Fall, Tove, Farrall, Martin, Felix, Janine F, Ferrières, Jean, Ferrucci, Luigi, Fornage, Myriam, and Forrester, Terrence
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CHARGE-EchoGen consortium ,CHARGE-HF consortium ,Wellcome Trust Case Control Consortium ,Cells ,Cultured ,Humans ,Hypertension ,Microarray Analysis ,Blood Pressure ,Polymorphism ,Single Nucleotide ,African Continental Ancestry Group ,Asian Continental Ancestry Group ,Genome-Wide Association Study ,Cells ,Cultured ,Polymorphism ,Single Nucleotide ,Developmental Biology ,Biological Sciences ,Medical and Health Sciences - Abstract
To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
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- 2016
31. 52 Genetic Loci Influencing Myocardial Mass
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van der Harst, Pim, van Setten, Jessica, Verweij, Niek, Vogler, Georg, Franke, Lude, Maurano, Matthew T, Wang, Xinchen, Leach, Irene Mateo, Eijgelsheim, Mark, Sotoodehnia, Nona, Hayward, Caroline, Sorice, Rossella, Meirelles, Osorio, Lyytikäinen, Leo-Pekka, Polašek, Ozren, Tanaka, Toshiko, Arking, Dan E, Ulivi, Sheila, Trompet, Stella, Müller-Nurasyid, Martina, Smith, Albert V, Dörr, Marcus, Kerr, Kathleen F, Magnani, Jared W, Del Greco M., Fabiola, Zhang, Weihua, Nolte, Ilja M, Silva, Claudia T, Padmanabhan, Sandosh, Tragante, Vinicius, Esko, Tõnu, Abecasis, Gonçalo R, Adriaens, Michiel E, Andersen, Karl, Barnett, Phil, Bis, Joshua C, Bodmer, Rolf, Buckley, Brendan M, Campbell, Harry, Cannon, Megan V, Chakravarti, Aravinda, Chen, Lin Y, Delitala, Alessandro, Devereux, Richard B, Doevendans, Pieter A, Dominiczak, Anna F, Ferrucci, Luigi, Ford, Ian, Gieger, Christian, Harris, Tamara B, Haugen, Eric, Heinig, Matthias, Hernandez, Dena G, Hillege, Hans L, Hirschhorn, Joel N, Hofman, Albert, Hubner, Norbert, Hwang, Shih-Jen, Iorio, Annamaria, Kähönen, Mika, Kellis, Manolis, Kolcic, Ivana, Kooner, Ishminder K, Kooner, Jaspal S, Kors, Jan A, Lakatta, Edward G, Lage, Kasper, Launer, Lenore J, Levy, Daniel, Lundby, Alicia, Macfarlane, Peter W, May, Dalit, Meitinger, Thomas, Metspalu, Andres, Nappo, Stefania, Naitza, Silvia, Neph, Shane, Nord, Alex S, Nutile, Teresa, Okin, Peter M, Olsen, Jesper V, Oostra, Ben A, Penninger, Josef M, Pennacchio, Len A, Pers, Tune H, Perz, Siegfried, Peters, Annette, Pinto, Yigal M, Pfeufer, Arne, Pilia, Maria Grazia, Pramstaller, Peter P, Prins, Bram P, Raitakari, Olli T, Raychaudhuri, Soumya, Rice, Ken M, Rossin, Elizabeth J, Rotter, Jerome I, Schafer, Sebastian, Schlessinger, David, and Schmidt, Carsten O
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Medical Physiology ,Biomedical and Clinical Sciences ,Genetics ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Heart Disease ,Biotechnology ,Human Genome ,2.1 Biological and endogenous factors ,Animals ,Cardiomegaly ,Genetic Loci ,Genome-Wide Association Study ,Humans ,electrocardiogram ,genetic association study ,heart failure ,left ventricular hypertrophy ,QRS ,Cardiorespiratory Medicine and Haematology ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundMyocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.ObjectivesThis meta-analysis sought to gain insights into the genetic determinants of myocardial mass.MethodsWe carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.ResultsWe identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo.ConclusionsTaken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.
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- 2016
32. Genome-wide association study identifies 74 loci associated with educational attainment
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Okbay, Aysu, Beauchamp, Jonathan P, Fontana, Mark Alan, Lee, James J, Pers, Tune H, Rietveld, Cornelius A, Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Meddens, S Fleur W, Oskarsson, Sven, Pickrell, Joseph K, Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Abdellaoui, Abdel, Ahluwalia, Tarunveer S, Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H, Pina Concas, Maria, Derringer, Jaime, Furlotte, Nicholas A, Galesloot, Tessel E, Girotto, Giorgia, Gupta, Richa, Hall, Leanne M, Harris, Sarah E, Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E, Kaasik, Kadri, Kalafati, Ioanna P, Karlsson, Robert, Kong, Augustine, Lahti, Jari, Lee, Sven J van der, deLeeuw, Christiaan, Lind, Penelope A, Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B, van der Most, Peter J, Oldmeadow, Christopher, Payton, Antony, Pervjakova, Natalia, Peyrot, Wouter J, Qian, Yong, Raitakari, Olli, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E, Shi, Jianxin, Smith, Albert V, Poot, Raymond A, St Pourcain, Beate, Teumer, Alexander, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Westra, Harm-Jan, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z, Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E, Biino, Ginevra, Bønnelykke, Klaus, Boyle, Patricia A, Campbell, Harry, Cappuccio, Francesco P, Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Panos, Demuth, Ilja, Ding, Jun, Eibich, Peter, Eisele, Lewin, Eklund, Niina, Evans, David M, Faul, Jessica D, Feitosa, Mary F, Forstner, Andreas J, Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V, Harris, Tamara B, Heath, Andrew C, Hocking, Lynne J, Holliday, Elizabeth G, Homuth, Georg, and Horan, Michael A
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Biological Sciences ,Genetics ,Epidemiology ,Health Sciences ,Statistics ,Mathematical Sciences ,Human Genome ,Clinical Research ,Alzheimer Disease ,Bipolar Disorder ,Brain ,Cognition ,Computational Biology ,Educational Status ,Fetus ,Gene Expression Regulation ,Gene-Environment Interaction ,Genome-Wide Association Study ,Humans ,Molecular Sequence Annotation ,Polymorphism ,Single Nucleotide ,Schizophrenia ,United Kingdom ,LifeLines Cohort Study ,General Science & Technology - Abstract
Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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- 2016
33. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci
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Ellinghaus, David, Jostins, Luke, Spain, Sarah L, Cortes, Adrian, Bethune, Jörn, Han, Buhm, Park, Yu Rang, Raychaudhuri, Soumya, Pouget, Jennie G, Hübenthal, Matthias, Folseraas, Trine, Wang, Yunpeng, Esko, Tonu, Metspalu, Andres, Westra, Harm-Jan, Franke, Lude, Pers, Tune H, Weersma, Rinse K, Collij, Valerie, D'Amato, Mauro, Halfvarson, Jonas, Jensen, Anders Boeck, Lieb, Wolfgang, Degenhardt, Franziska, Forstner, Andreas J, Hofmann, Andrea, Schreiber, Stefan, Mrowietz, Ulrich, Juran, Brian D, Lazaridis, Konstantinos N, Brunak, Søren, Dale, Anders M, Trembath, Richard C, Weidinger, Stephan, Weichenthal, Michael, Ellinghaus, Eva, Elder, James T, Barker, Jonathan NWN, Andreassen, Ole A, McGovern, Dermot P, Karlsen, Tom H, Barrett, Jeffrey C, Parkes, Miles, Brown, Matthew A, and Franke, Andre
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Biological Sciences ,Genetics ,Prevention ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Bayes Theorem ,Cholangitis ,Sclerosing ,Chronic Disease ,Colitis ,Ulcerative ,Comorbidity ,Crohn Disease ,Genetic Heterogeneity ,Genetic Pleiotropy ,Genetic Variation ,Genome-Wide Association Study ,Genotype ,Humans ,Inflammation ,Psoriasis ,Quantitative Trait Loci ,Spondylitis ,Ankylosing ,International IBD Genetics Consortium ,International Genetics of Ankylosing Spondylitis Consortium ,International PSC Study Group ,Genetic Analysis of Psoriasis Consortium ,Psoriasis Association Genetics Extension ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.
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- 2016
34. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.
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Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Del Greco M, Fabiola, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton JN, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, and Savage, David B
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Adipose Tissue ,Animals ,Mice ,Leptin ,RNA ,Messenger ,Tissue Culture Techniques ,Gene Expression Regulation ,Male ,Genome-Wide Association Study ,Gene Knockdown Techniques ,RNA ,Messenger - Abstract
Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P
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- 2016
35. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.
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Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y, Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H, Johnson, Andrew D, Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F, Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B, Nolte, Ilja M, van der Most, Peter J, Wright, Alan F, Shuldiner, Alan R, Morrison, Alanna C, Hofman, Albert, Smith, Albert V, Dreisbach, Albert W, Franke, Andre, Uitterlinden, Andre G, Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I, Ponte, Belen, Oostra, Ben A, Paulweber, Bernhard, Krämer, Bernhard K, Mitchell, Braxton D, Buckley, Brendan M, Peralta, Carmen A, Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N, Shaffer, Christian M, Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M, Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S, Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J, Holliday, Elizabeth G, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B, Navis, Gerjan J, Curhan, Gary C, Ehret, George B, Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W, Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, and Schmidt, Helena
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ICBP Consortium ,AGEN Consortium ,CARDIOGRAM ,CHARGe-Heart Failure Group ,ECHOGen Consortium ,Humans ,Genetic Predisposition to Disease ,Gene Expression Regulation ,Genotype ,Renal Insufficiency ,Chronic ,Genome-Wide Association Study ,Renal Insufficiency ,Chronic - Abstract
Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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- 2016
36. Modeling neural tube development by differentiation of human embryonic stem cells in a microfluidic WNT gradient
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Rifes, Pedro, Isaksson, Marc, Rathore, Gaurav Singh, Aldrin-Kirk, Patrick, Møller, Oliver Knights, Barzaghi, Guido, Lee, Julie, Egerod, Kristoffer Lihme, Rausch, Dylan M., Parmar, Malin, Pers, Tune H., Laurell, Thomas, and Kirkeby, Agnete
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- 2020
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- View/download PDF
37. Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores
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Vilhjálmsson, Bjarni J, Yang, Jian, Finucane, Hilary K, Gusev, Alexander, Lindström, Sara, Ripke, Stephan, Genovese, Giulio, Loh, Po-Ru, Bhatia, Gaurav, Do, Ron, Hayeck, Tristan, Won, Hong-Hee, Consortium, Schizophrenia Working Group of the Psychiatric Genomics, Neale, Benjamin M, Corvin, Aiden, Walters, James TR, Farh, Kai-How, Holmans, Peter A, Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A, Huang, Hailiang, Pers, Tune H, Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A, Begemann, Martin, Belliveau, Richard A, Bene, Judit, Bergen, Sarah E, Bevilacqua, Elizabeth, Bigdeli, Tim B, Black, Donald W, Bruggeman, Richard, Buccola, Nancy G, Buckner, Randy L, Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M, Carr, Vaughan J, Carrera, Noa, Catts, Stanley V, Chambert, Kimberly D, Chan, Raymond CK, Chen, Ronald YL, Chen, Eric YH, Cheng, Wei, Cheung, Eric FC, Chong, Siow Ann, Cloninger, C Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J, Curtis, David, Davidson, Michael, Davis, Kenneth L, Degenhardt, Franziska, Del Favero, Jurgen, DeLisi, Lynn E, Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Fanous, Ayman H, Farrell, Martilias S, Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B, Friedl, Marion, Friedman, Joseph I, Fromer, Menachem, Georgieva, Lyudmila, Gershon, Elliot S, Giegling, Ina, Giusti-Rodrguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I, Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, and Grove, Jakob
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Schizophrenia ,Mental Health ,Brain Disorders ,Serious Mental Illness ,Genome-Wide Association Study ,Genotype ,Humans ,Linkage Disequilibrium ,Models ,Theoretical ,Multifactorial Inheritance ,Multiple Sclerosis ,Phenotype ,Polymorphism ,Single Nucleotide ,Prognosis ,Quantitative Trait Loci ,Schizophrenia Working Group of the Psychiatric Genomics Consortium ,Discovery ,Biology ,and Risk of Inherited Variants in Breast Cancer (DRIVE) study ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R(2) increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase.
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- 2015
38. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.
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Winkler, Thomas W, Justice, Anne E, Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F, Chu, Su, Czajkowski, Jacek, Esko, Tõnu, Fall, Tove, Kilpeläinen, Tuomas O, Lu, Yingchang, Mägi, Reedik, Mihailov, Evelin, Pers, Tune H, Rüeger, Sina, Teumer, Alexander, Ehret, Georg B, Ferreira, Teresa, Heard-Costa, Nancy L, Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D, Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M, Jansen, Rick, Westra, Harm-Jan, White, Charles C, Absher, Devin, Ahluwalia, Tarunveer S, Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L, de Craen, Anton JM, Bis, Joshua C, Bonnefond, Amélie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston WK, Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E, Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B, Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E, Jackson, Anne U, Jacobs, Kevin B, Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E, Lahti, Jari, Mateo Leach, Irene, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela AF, Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L, Montasser, May E, Müller, Gabriele, Müller-Nurasyid, Martina, Nolte, Ilja M, Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W, Renström, Frida, Rizzi, Federica, Rose, Lynda M, Ryan, Kathy A, Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stančáková, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J, Sung, Yun Ju, and Tachmazidou, Ioanna
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CHARGE Consortium ,DIAGRAM Consortium ,GLGC Consortium ,Global-BPGen Consortium ,ICBP Consortium ,MAGIC Consortium ,Humans ,Genetic Predisposition to Disease ,Body Mass Index ,Body Size ,Waist-Hip Ratio ,Chromosome Mapping ,Age Factors ,Sex Characteristics ,Polymorphism ,Single Nucleotide ,Adult ,Aged ,Middle Aged ,European Continental Ancestry Group ,Female ,Male ,Genome-Wide Association Study ,Developmental Biology ,Genetics - Abstract
Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR
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- 2015
39. Genome-wide Analysis of Body Proportion Classifies Height-Associated Variants by Mechanism of Action and Implicates Genes Important for Skeletal Development
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Chan, Yingleong, Salem, Rany M, Hsu, Yu-Han H, McMahon, George, Pers, Tune H, Vedantam, Sailaja, Esko, Tonu, Guo, Michael H, Lim, Elaine T, Consortium, GIANT, Franke, Lude, Smith, George Davey, Strachan, David P, and Hirschhorn, Joel N
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Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Adult ,Black or African American ,Body Height ,Chromosome Mapping ,Female ,Genome-Wide Association Study ,Humans ,Leg Bones ,Male ,Middle Aged ,Multifactorial Inheritance ,Phenotype ,Polymorphism ,Single Nucleotide ,White People ,GIANT Consortium ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Human height is a composite measurement, reflecting the sum of leg, spine, and head lengths. Many common variants influence total height, but the effects of these or other variants on the components of height (body proportion) remain largely unknown. We studied sitting height ratio (SHR), the ratio of sitting height to total height, to identify such effects in 3,545 African Americans and 21,590 individuals of European ancestry. We found that SHR is heritable: 26% and 39% of the total variance of SHR can be explained by common variants in European and African Americans, respectively, and global European admixture is negatively correlated with SHR in African Americans (r(2) ≈ 0.03). Six regions reached genome-wide significance (p < 5 × 10(-8)) for association with SHR and overlapped biological candidate genes, including TBX2 and IGFBP3. We found that 130 of 670 height-associated variants are nominally associated (p < 0.05) with SHR, more than expected by chance (p = 5 × 10(-40)). At these 130 loci, the height-increasing alleles are associated with either a decrease (71 loci) or increase (59 loci) in SHR, suggesting that different height loci disproportionally affect either leg length or spine/head length. Pathway analyses via DEPICT revealed that height loci affecting SHR, and especially those affecting leg length, show enrichment of different biological pathways (e.g., bone/cartilage/growth plate pathways) than do loci with no effect on SHR (e.g., embryonic development). These results highlight the value of using a pair of related but orthogonal phenotypes, in this case SHR with height, as a prism to dissect the biology underlying genetic associations in polygenic traits and diseases.
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- 2015
40. New genetic loci link adipose and insulin biology to body fat distribution
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Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Locke, Adam E, Mägi, Reedik, Strawbridge, Rona J, Pers, Tune H, Fischer, Krista, Justice, Anne E, Workalemahu, Tsegaselassie, Wu, Joseph MW, Buchkovich, Martin L, Heard-Costa, Nancy L, Roman, Tamara S, Drong, Alexander W, Song, Ci, Gustafsson, Stefan, Day, Felix R, Esko, Tonu, Fall, Tove, Kutalik, Zoltán, Luan, Jian’an, Randall, Joshua C, Scherag, André, Vedantam, Sailaja, Wood, Andrew R, Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M, Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L, Buyske, Steven, Demirkan, Ayse, Ehret, Georg B, Feitosa, Mary F, Goel, Anuj, Jackson, Anne U, Johnson, Toby, Kleber, Marcus E, Kristiansson, Kati, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J, Prokopenko, Inga, Stančáková, Alena, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V, Yengo, Loïc, Zhang, Weihua, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M, Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blüher, Matthias, Böhringer, Stefan, Bonnet, Fabrice, Böttcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B, Caspersen, Ida H, Clarke, Robert, Warwick Daw, E, Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex SF, Eklund, Niina, Erdos, Michael R, Estrada, Karol, Eury, Elodie, Friedrich, Nele, Garcia, Melissa E, Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S, Golay, Alain, Grallert, Harald, Grammer, Tanja B, Gräßler, Jürgen, Grewal, Jagvir, Groves, Christopher J, Haller, Toomas, and Hallmans, Goran
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Genetics ,Human Genome ,Diabetes ,Obesity ,Nutrition ,2.1 Biological and endogenous factors ,Aetiology ,Metabolic and endocrine ,Cardiovascular ,Stroke ,Adipocytes ,Adipogenesis ,Adipose Tissue ,Age Factors ,Body Fat Distribution ,Body Mass Index ,Epigenesis ,Genetic ,Europe ,Female ,Genome ,Human ,Genome-Wide Association Study ,Humans ,Insulin ,Insulin Resistance ,Male ,Models ,Biological ,Neovascularization ,Physiologic ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Racial Groups ,Sex Characteristics ,Transcription ,Genetic ,Waist-Hip Ratio ,ADIPOGen Consortium ,CARDIOGRAMplusC4D Consortium ,CKDGen Consortium ,GEFOS Consortium ,GENIE Consortium ,GLGC ,ICBP ,International Endogene Consortium ,LifeLines Cohort Study ,MAGIC Investigators ,MuTHER Consortium ,PAGE Consortium ,ReproGen Consortium ,General Science & Technology - Abstract
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P
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- 2015
41. Genetic studies of body mass index yield new insights for obesity biology
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Locke, Adam E, Kahali, Bratati, Berndt, Sonja I, Justice, Anne E, Pers, Tune H, Day, Felix R, Powell, Corey, Vedantam, Sailaja, Buchkovich, Martin L, Yang, Jian, Croteau-Chonka, Damien C, Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Kutalik, Zoltán, Luan, Jian’an, Mägi, Reedik, Randall, Joshua C, Winkler, Thomas W, Wood, Andrew R, Workalemahu, Tsegaselassie, Faul, Jessica D, Smith, Jennifer A, Hua Zhao, Jing, Zhao, Wei, Chen, Jin, Fehrmann, Rudolf, Hedman, Åsa K, Karjalainen, Juha, Schmidt, Ellen M, Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bolton, Jennifer L, Bragg-Gresham, Jennifer L, Buyske, Steven, Demirkan, Ayse, Deng, Guohong, Ehret, Georg B, Feenstra, Bjarke, Feitosa, Mary F, Fischer, Krista, Goel, Anuj, Gong, Jian, Jackson, Anne U, Kanoni, Stavroula, Kleber, Marcus E, Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Medland, Sarah E, Nalls, Michael A, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J, Prokopenko, Inga, Shungin, Dmitry, Stančáková, Alena, Strawbridge, Rona J, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van Setten, Jessica, Van Vliet-Ostaptchouk, Jana V, Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Isaacs, Aaron, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M, Attwood, Antony P, Bandinelli, Stefania, Barrett, Amy, Bas, Isabelita N, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blagieva, Roza, Blüher, Matthias, Böhringer, Stefan, Bonnycastle, Lori L, Böttcher, Yvonne, Boyd, Heather A, Bruinenberg, Marcel, Caspersen, Ida H, Ida Chen, Yii-Der, Clarke, Robert, Warwick Daw, E, de Craen, Anton JM, Delgado, Graciela, and Dimitriou, Maria
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Nutrition ,Obesity ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,Stroke ,Cardiovascular ,Metabolic and endocrine ,Oral and gastrointestinal ,Cancer ,Adipogenesis ,Adiposity ,Age Factors ,Body Mass Index ,Energy Metabolism ,Europe ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Glutamic Acid ,Humans ,Insulin ,Insulin Secretion ,Male ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Racial Groups ,Synapses ,LifeLines Cohort Study ,ADIPOGen Consortium ,AGEN-BMI Working Group ,CARDIOGRAMplusC4D Consortium ,CKDGen Consortium ,GLGC ,ICBP ,MAGIC Investigators ,MuTHER Consortium ,MIGen Consortium ,PAGE Consortium ,ReproGen Consortium ,GENIE Consortium ,International Endogene Consortium ,General Science & Technology - Abstract
Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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- 2015
42. Defining the role of common variation in the genomic and biological architecture of adult human height
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Wood, Andrew R, Esko, Tonu, Yang, Jian, Vedantam, Sailaja, Pers, Tune H, Gustafsson, Stefan, Chu, Audrey Y, Estrada, Karol, Luan, Jian'an, Kutalik, Zoltán, Amin, Najaf, Buchkovich, Martin L, Croteau-Chonka, Damien C, Day, Felix R, Duan, Yanan, Fall, Tove, Fehrmann, Rudolf, Ferreira, Teresa, Jackson, Anne U, Karjalainen, Juha, Lo, Ken Sin, Locke, Adam E, Mägi, Reedik, Mihailov, Evelin, Porcu, Eleonora, Randall, Joshua C, Scherag, André, Vinkhuyzen, Anna AE, Westra, Harm-Jan, Winkler, Thomas W, Workalemahu, Tsegaselassie, Zhao, Jing Hua, Absher, Devin, Albrecht, Eva, Anderson, Denise, Baron, Jeffrey, Beekman, Marian, Demirkan, Ayse, Ehret, Georg B, Feenstra, Bjarke, Feitosa, Mary F, Fischer, Krista, Fraser, Ross M, Goel, Anuj, Gong, Jian, Justice, Anne E, Kanoni, Stavroula, Kleber, Marcus E, Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Lui, Julian C, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Nalls, Michael A, Nyholt, Dale R, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Prokopenko, Inga, Ried, Janina S, Ripke, Stephan, Shungin, Dmitry, Stancáková, Alena, Strawbridge, Rona J, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van Setten, Jessica, Van Vliet-Ostaptchouk, Jana V, Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Afzal, Uzma, Ärnlöv, Johan, Arscott, Gillian M, Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blüher, Matthias, Bolton, Jennifer L, Böttcher, Yvonne, Boyd, Heather A, Bruinenberg, Marcel, Buckley, Brendan M, Buyske, Steven, Caspersen, Ida H, Chines, Peter S, Clarke, Robert, Claudi-Boehm, Simone, Cooper, Matthew, Daw, E Warwick, De Jong, Pim A, Deelen, Joris, and Delgado, Graciela
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Biological Sciences ,Genetics ,Biotechnology ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Adult ,Analysis of Variance ,Body Height ,Genetic Variation ,Genetics ,Population ,Genome-Wide Association Study ,Humans ,Oligonucleotide Array Sequence Analysis ,Polymorphism ,Single Nucleotide ,White People ,Electronic Medical Records and Genomics (eMEMERGEGE) Consortium ,MIGen Consortium ,PAGEGE Consortium ,LifeLines Cohort Study ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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- 2014
43. Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases
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Gusev, Alexander, Lee, S Hong, Trynka, Gosia, Finucane, Hilary, Vilhjálmsson, Bjarni J, Xu, Han, Zang, Chongzhi, Ripke, Stephan, Bulik-Sullivan, Brendan, Stahl, Eli, Kähler, Anna K, Hultman, Christina M, Purcell, Shaun M, McCarroll, Steven A, Daly, Mark J, Pasaniuc, Bogdan, Sullivan, Patrick F, Neale, Benjamin M, Wray, Naomi R, Raychaudhuri, Soumya, Price, Alkes, Corvin, Aiden, Walters, James TR, Farh, Kai-How, Holmans, Peter A, Lee, Phil, Collier, David A, Huang, Hailiang, Pers, Tune H, Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A, Begemann, Martin, Belliveau, Richard A, Bene, Judit, Bergen, Sarah E, Bevilacqua, Elizabeth, Bigdeli, Tim B, Black, Donald W, Børglum, Anders D, Bruggeman, Richard, Buccola, Nancy G, Buckner, Randy L, Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M, Carr, Vaughan J, Carrera, Noa, Catts, Stanley V, Chambert, Kimberly D, Chan, Raymond CK, Chen, Ronald YL, Chen, Eric YH, Cheng, Wei, Cheung, Eric FC, Chong, Siow Ann, Cloninger, C Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J, Curtis, David, Davidson, Michael, Davis, Kenneth L, Degenhardt, Franziska, Del Favero, Jurgen, DeLisi, Lynn E, Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Fanous, Ayman H, Farrell, Martilias S, Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B, Friedl, Marion, Friedman, Joseph I, Fromer, Menachem, Genovese, Giulio, and Georgieva, Lyudmila
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Prevention ,Computer Simulation ,Genetic Diseases ,Inborn ,Genetic Variation ,Genome-Wide Association Study ,Humans ,Inheritance Patterns ,Models ,Genetic ,Open Reading Frames ,Regulatory Elements ,Transcriptional ,Schizophrenia Working Group of the Psychiatric Genomics Consortium ,SWE-SCZ Consortium ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs (hg(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg(2) from imputed SNPs (5.1× enrichment; p = 3.7 × 10(-17)) and 38% (SE = 4%) of hg(2) from genotyped SNPs (1.6× enrichment, p = 1.0 × 10(-4)). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained
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- 2014
44. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche
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Perry, John RB, Day, Felix, Elks, Cathy E, Sulem, Patrick, Thompson, Deborah J, Ferreira, Teresa, He, Chunyan, Chasman, Daniel I, Esko, Tõnu, Thorleifsson, Gudmar, Albrecht, Eva, Ang, Wei Q, Corre, Tanguy, Cousminer, Diana L, Feenstra, Bjarke, Franceschini, Nora, Ganna, Andrea, Johnson, Andrew D, Kjellqvist, Sanela, Lunetta, Kathryn L, McMahon, George, Nolte, Ilja M, Paternoster, Lavinia, Porcu, Eleonora, Smith, Albert V, Stolk, Lisette, Teumer, Alexander, Tšernikova, Natalia, Tikkanen, Emmi, Ulivi, Sheila, Wagner, Erin K, Amin, Najaf, Bierut, Laura J, Byrne, Enda M, Hottenga, Jouke-Jan, Koller, Daniel L, Mangino, Massimo, Pers, Tune H, Yerges-Armstrong, Laura M, Hua Zhao, Jing, Andrulis, Irene L, Anton-Culver, Hoda, Atsma, Femke, Bandinelli, Stefania, Beckmann, Matthias W, Benitez, Javier, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Buring, Julie E, Chang-Claude, Jenny, Chanock, Stephen, Chen, Jinhui, Chenevix-Trench, Georgia, Collée, J Margriet, Couch, Fergus J, Couper, David, Coviello, Andrea D, Cox, Angela, Czene, Kamila, D’adamo, Adamo Pio, Davey Smith, George, De Vivo, Immaculata, Demerath, Ellen W, Dennis, Joe, Devilee, Peter, Dieffenbach, Aida K, Dunning, Alison M, Eiriksdottir, Gudny, Eriksson, Johan G, Fasching, Peter A, Ferrucci, Luigi, Flesch-Janys, Dieter, Flyger, Henrik, Foroud, Tatiana, Franke, Lude, Garcia, Melissa E, García-Closas, Montserrat, Geller, Frank, de Geus, Eco EJ, Giles, Graham G, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Guénel, Pascal, Guo, Suiqun, Hall, Per, Hamann, Ute, Haring, Robin, Hartman, Catharina A, Heath, Andrew C, Hofman, Albert, Hooning, Maartje J, Hopper, John L, Hu, Frank B, Hunter, David J, Karasik, David, and Kiel, Douglas P
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Paediatrics ,Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Contraception/Reproduction ,Pediatric ,Biotechnology ,Human Genome ,Clinical Research ,Adolescent ,Age Factors ,Alleles ,Body Mass Index ,Breast Neoplasms ,Calcium-Binding Proteins ,Cardiovascular Diseases ,Child ,Diabetes Mellitus ,Type 2 ,Europe ,Female ,Genetic Loci ,Genome-Wide Association Study ,Genomic Imprinting ,Humans ,Hypothalamo-Hypophyseal System ,Intercellular Signaling Peptides and Proteins ,Male ,Membrane Proteins ,Menarche ,Obesity ,Ovary ,Parents ,Polymorphism ,Single Nucleotide ,Potassium Channels ,Tandem Pore Domain ,Proteins ,Quantitative Trait Loci ,Receptors ,GABA-B ,Receptors ,Retinoic Acid ,Ribonucleoproteins ,Ubiquitin-Protein Ligases ,Australian Ovarian Cancer Study ,GENICA Network ,kConFab ,LifeLines Cohort Study ,InterAct Consortium ,Early Growth Genetics (EGG) Consortium ,General Science & Technology - Abstract
Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P
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- 2014
45. Biological insights from 108 schizophrenia-associated genetic loci
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Ripke, Stephan, Neale, Benjamin M, Corvin, Aiden, Walters, James TR, Farh, Kai-How, Holmans, Peter A, Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A, Huang, Hailiang, Pers, Tune H, Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A, Begemann, Martin, Belliveau, Richard A Jr, Bene, Judit, Bergen, Sarah E, Bevilacqua, Elizabeth, Bigdeli, Tim B, Black, Donald W, Bruggeman, Richard, Buccola, Nancy G, Buckner, Randy L, Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M, Carr, Vaughan J, Carrera, Noa, Catts, Stanley V, Chambert, Kimberly D, Chan, Raymond CK, Chen, Ronald YL, Chen, Eric YH, Cheng, Wei, Cheung, Eric FC, Chong, Siow Ann, Cloninger, C Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J, Curtis, David, Davidson, Michael, Davis, Kenneth L, Degenhardt, Franziska, Del Favero, Jurgen, Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Fanous, Ayman H, Farrell, Martilias S, Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B, Friedl, Marion, Friedman, Joseph I, Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Giegling, Ina, Giusti-Rodriguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I, Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, de Haan, Lieuwe, Hammer, Christian, Hamshere, Marian L, Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Hartmann, Annette M, Henskens, Frans A, Herms, Stefan, Hirschhorn, Joel N, Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V, Hougaard, David M, Ikeda, Masashi, and Joa, Inge
- Subjects
Human Genome ,Brain Disorders ,Serious Mental Illness ,Prevention ,Schizophrenia ,Genetics ,Neurosciences ,Mental Health ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Alleles ,Brain ,Enhancer Elements ,Genetic ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Glutamic Acid ,Humans ,Immunity ,Multifactorial Inheritance ,Mutation ,Odds Ratio ,Polymorphism ,Single Nucleotide ,Synaptic Transmission ,Schizophrenia Working Group of the Psychiatric Genomics Consortium ,General Science & Technology - Abstract
Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
- Published
- 2014
46. Whole-Exome Sequencing of 2,000 Danish Individuals and the Role of Rare Coding Variants in Type 2 Diabetes
- Author
-
Lohmueller, Kirk E, Sparsø, Thomas, Li, Qibin, Andersson, Ehm, Korneliussen, Thorfinn, Albrechtsen, Anders, Banasik, Karina, Grarup, Niels, Hallgrimsdottir, Ingileif, Kiil, Kristoffer, Kilpeläinen, Tuomas O, Krarup, Nikolaj T, Pers, Tune H, Sanchez, Gaston, Hu, Youna, DeGiorgio, Michael, Jørgensen, Torben, Sandbæk, Annelli, Lauritzen, Torsten, Brunak, Søren, Kristiansen, Karsten, Li, Yingrui, Hansen, Torben, Wang, Jun, Nielsen, Rasmus, and Pedersen, Oluf
- Subjects
Biological Sciences ,Genetics ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Published
- 2014
47. Molecular Connectomics Reveals a Glucagon-Like Peptide 1 Sensitive Neural Circuit for Satiety
- Author
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Webster, Addison N., primary, Becker, Jordan J., additional, Li, Chia, additional, Schwalbe, Dana C., additional, Kerspern, Damien, additional, Karolczak, Eva O., additional, Godschall, Elizabeth N., additional, Belmont-Rausch, Dylan Matthew, additional, Pers, Tune H., additional, Lutas, Andrew, additional, Habib, Naomi, additional, Güler, Ali D., additional, Krashes, Michael J., additional, and Campbell, John N., additional
- Published
- 2023
- Full Text
- View/download PDF
48. Molecular consequences of peripheral Influenza A infection on cell populations in the murine hypothalamus
- Author
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Lemcke, René, primary, Egebjerg, Christine, additional, Berendtsen, Nicolai T, additional, Egerod, Kristoffer L, additional, Thomsen, Allan R, additional, Pers, Tune H, additional, Christensen, Jan P, additional, and Kornum, Birgitte R, additional
- Published
- 2023
- Full Text
- View/download PDF
49. Author Response:: Molecular consequences of peripheral Influenza A infection on cell populations in the murine hypothalamus
- Author
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Lemcke, René, primary, Egebjerg, Christine, additional, Berendtsen, Nicolai Tubæk, additional, Egerod, Kristoffer Lihme, additional, Thomsen, Allan Randrup, additional, Pers, Tune H, additional, Christensen, Jan Pravsgaard, additional, and Kornum, Birgitte Rahbek, additional
- Published
- 2023
- Full Text
- View/download PDF
50. Whole-Exome Sequencing of 2,000 Danish Individuals and the Role of Rare Coding Variants in Type 2 Diabetes
- Author
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Lohmueller, Kirk E, Sparsø, Thomas, Li, Qibin, Andersson, Ehm, Korneliussen, Thorfinn, Albrechtsen, Anders, Banasik, Karina, Grarup, Niels, Hallgrimsdottir, Ingileif, Kiil, Kristoffer, Kilpeläinen, Tuomas O, Krarup, Nikolaj T, Pers, Tune H, Sanchez, Gaston, Hu, Youna, DeGiorgio, Michael, Jørgensen, Torben, Sandbæk, Annelli, Lauritzen, Torsten, Brunak, Søren, Kristiansen, Karsten, Li, Yingrui, Hansen, Torben, Wang, Jun, Nielsen, Rasmus, and Pedersen, Oluf
- Subjects
Human Genome ,Genetic Testing ,Diabetes ,Biotechnology ,Cardiovascular ,Genetics ,Autoimmune Disease ,Aetiology ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Computational Biology ,Denmark ,Diabetes Mellitus ,Type 2 ,Exome ,Genetic Association Studies ,Genetic Variation ,Genotype ,High-Throughput Nucleotide Sequencing ,Humans ,Models ,Statistical ,Open Reading Frames ,Polymorphism ,Single Nucleotide ,White People ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
It has been hypothesized that, in aggregate, rare variants in coding regions of genes explain a substantial fraction of the heritability of common diseases. We sequenced the exomes of 1,000 Danish cases with common forms of type 2 diabetes (including body mass index > 27.5 kg/m(2) and hypertension) and 1,000 healthy controls to an average depth of 56×. Our simulations suggest that our study had the statistical power to detect at least one causal gene (a gene containing causal mutations) if the heritability of these common diseases was explained by rare variants in the coding regions of a limited number of genes. We applied a series of gene-based tests to detect such susceptibility genes. However, no gene showed a significant association with disease risk after we corrected for the number of genes analyzed. Thus, we could reject a model for the genetic architecture of type 2 diabetes where rare nonsynonymous variants clustered in a modest number of genes (fewer than 20) are responsible for the majority of disease risk.
- Published
- 2013
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