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1. The Queensland Twin Adolescent Brain Project, a longitudinal study of adolescent brain development

Author: Lachlan T. Strike, Narelle K. Hansell, Kai-Hsiang Chuang, Jessica L. Miller, Greig I. de Zubicaray, Paul M. Thompson, Katie L. McMahon, and Margaret J. Wright
Subjects: Science
Abstract: Abstract We describe the Queensland Twin Adolescent Brain (QTAB) dataset and provide a detailed methodology and technical validation to facilitate data usage. The QTAB dataset comprises multimodal neuroimaging, as well as cognitive and mental health data collected in adolescent twins over two sessions (session 1: N = 422, age 9–14 years; session 2: N = 304, 10–16 years). The MRI protocol consisted of T1-weighted (MP2RAGE), T2-weighted, FLAIR, high-resolution TSE, SWI, resting-state fMRI, DWI, and ASL scans. Two fMRI tasks were added in session 2: an emotional conflict task and a passive movie-watching task. Outside of the scanner, we assessed cognitive function using standardised tests. We also obtained self-reports of symptoms for anxiety and depression, perceived stress, sleepiness, pubertal development measures, and risk and protective factors. We additionally collected several biological samples for genomic and metagenomic analysis. The QTAB project was established to promote health-related research in adolescence.
Published: 2023
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2. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Gail Davies, Max Lam, Sarah E. Harris, Joey W. Trampush, Michelle Luciano, W. David Hill, Saskia P. Hagenaars, Stuart J. Ritchie, Riccardo E. Marioni, Chloe Fawns-Ritchie, David C. M. Liewald, Judith A. Okely, Ari V. Ahola-Olli, Catriona L. K. Barnes, Lars Bertram, Joshua C. Bis, Katherine E. Burdick, Andrea Christoforou, Pamela DeRosse, Srdjan Djurovic, Thomas Espeseth, Stella Giakoumaki, Sudheer Giddaluru, Daniel E. Gustavson, Caroline Hayward, Edith Hofer, M. Arfan Ikram, Robert Karlsson, Emma Knowles, Jari Lahti, Markus Leber, Shuo Li, Karen A. Mather, Ingrid Melle, Derek Morris, Christopher Oldmeadow, Teemu Palviainen, Antony Payton, Raha Pazoki, Katja Petrovic, Chandra A. Reynolds, Muralidharan Sargurupremraj, Markus Scholz, Jennifer A. Smith, Albert V. Smith, Natalie Terzikhan, Anbupalam Thalamuthu, Stella Trompet, Sven J. van der Lee, Erin B. Ware, B. Gwen Windham, Margaret J. Wright, Jingyun Yang, Jin Yu, David Ames, Najaf Amin, Philippe Amouyel, Ole A. Andreassen, Nicola J. Armstrong, Amelia A. Assareh, John R. Attia, Deborah Attix, Dimitrios Avramopoulos, David A. Bennett, Anne C. Böhmer, Patricia A. Boyle, Henry Brodaty, Harry Campbell, Tyrone D. Cannon, Elizabeth T. Cirulli, Eliza Congdon, Emily Drabant Conley, Janie Corley, Simon R. Cox, Anders M. Dale, Abbas Dehghan, Danielle Dick, Dwight Dickinson, Johan G. Eriksson, Evangelos Evangelou, Jessica D. Faul, Ian Ford, Nelson A. Freimer, He Gao, Ina Giegling, Nathan A. Gillespie, Scott D. Gordon, Rebecca F. Gottesman, Michael E. Griswold, Vilmundur Gudnason, Tamara B. Harris, Annette M. Hartmann, Alex Hatzimanolis, Gerardo Heiss, Elizabeth G. Holliday, Peter K. Joshi, Mika Kähönen, Sharon L. R. Kardia, Ida Karlsson, Luca Kleineidam, David S. Knopman, Nicole A. Kochan, Bettina Konte, John B. Kwok, Stephanie Le Hellard, Teresa Lee, Terho Lehtimäki, Shu-Chen Li, Christina M. Lill, Tian Liu, Marisa Koini, Edythe London, Will T. Longstreth, Oscar L. Lopez, Anu Loukola, Tobias Luck, Astri J. Lundervold, Anders Lundquist, Leo-Pekka Lyytikäinen, Nicholas G. Martin, Grant W. Montgomery, Alison D. Murray, Anna C. Need, Raymond Noordam, Lars Nyberg, William Ollier, Goran Papenberg, Alison Pattie, Ozren Polasek, Russell A. Poldrack, Bruce M. Psaty, Simone Reppermund, Steffi G. Riedel-Heller, Richard J. Rose, Jerome I. Rotter, Panos Roussos, Suvi P. Rovio, Yasaman Saba, Fred W. Sabb, Perminder S. Sachdev, Claudia L. Satizabal, Matthias Schmid, Rodney J. Scott, Matthew A. Scult, Jeannette Simino, P. Eline Slagboom, Nikolaos Smyrnis, Aïcha Soumaré, Nikos C. Stefanis, David J. Stott, Richard E. Straub, Kjetil Sundet, Adele M. Taylor, Kent D. Taylor, Ioanna Tzoulaki, Christophe Tzourio, André Uitterlinden, Veronique Vitart, Aristotle N. Voineskos, Jaakko Kaprio, Michael Wagner, Holger Wagner, Leonie Weinhold, K. Hoyan Wen, Elisabeth Widen, Qiong Yang, Wei Zhao, Hieab H. H. Adams, Dan E. Arking, Robert M. Bilder, Panos Bitsios, Eric Boerwinkle, Ornit Chiba-Falek, Aiden Corvin, Philip L. De Jager, Stéphanie Debette, Gary Donohoe, Paul Elliott, Annette L. Fitzpatrick, Michael Gill, David C. Glahn, Sara Hägg, Narelle K. Hansell, Ahmad R. Hariri, M. Kamran Ikram, J. Wouter Jukema, Eero Vuoksimaa, Matthew C. Keller, William S. Kremen, Lenore Launer, Ulman Lindenberger, Aarno Palotie, Nancy L. Pedersen, Neil Pendleton, David J. Porteous, Katri Räikkönen, Olli T. Raitakari, Alfredo Ramirez, Ivar Reinvang, Igor Rudan, Dan Rujescu, Reinhold Schmidt, Helena Schmidt, Peter W. Schofield, Peter R. Schofield, John M. Starr, Vidar M. Steen, Julian N. Trollor, Steven T. Turner, Cornelia M. Van Duijn, Arno Villringer, Daniel R. Weinberger, David R. Weir, James F. Wilson, Anil Malhotra, Andrew M. McIntosh, Catharine R. Gale, Sudha Seshadri, Thomas H. Mosley, Jan Bressler, Todd Lencz, and Ian J. Deary
Subjects: Science
Abstract: Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.
Published: 2019
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3. Region-specific sex differences in the hippocampus

Author: Liza van Eijk, Narelle K. Hansell, Lachlan T. Strike, Baptiste Couvy-Duchesne, Greig I. de Zubicaray, Paul M. Thompson, Katie L. McMahon, Brendan P. Zietsch, and Margaret J. Wright
Subjects: Hippocampus, Hippocampal subfields, Volume, Sex, Gender, Controlling methods, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: The hippocampus is a brain region critical for learning and memory, and is also implicated in several neuropsychiatric disorders that show sex differences in prevalence, symptom expression, and mean age of onset. On average, males have larger hippocampal volumes than females, but findings are inconclusive after adjusting for overall brain size. Although the hippocampus is a heterogenous structure, few studies have focused on sex differences in the hippocampal subfields – with little consensus on whether there are regionally specific sex differences in the hippocampus after adjusting for brain size, or whether it is important to adjust for total hippocampal volume (HPV). Here, using two young adult cohorts from the Queensland Twin IMaging study (QTIM; N = 727) and the Human Connectome Project (HCP; N = 960), we examined differences between males and females in the volumes of 12 hippocampal subfields, extracted using FreeSurfer 6.0. After adjusting the subfield volumes for either HPV or brain size (brain segmentation volume (BSV)) using four controlling methods (allometric, covariate, residual and matching), we estimated the percentage difference of the sex effect (males versus females) and Cohen’s d using hierarchical general linear models. Males had larger volumes compared to females in the parasubiculum (up to 6.04%; Cohen’s d = 0.46) and fimbria (up to 8.75%; d = 0.54) after adjusting for HPV. These sex differences were robust across the two cohorts and multiple controlling methods, though within cohort effect sizes were larger for the matched approach, due to the smaller sub-sample. Additional sex effects were identified in the HCP cohort and combined (QTIM and HCP) sample (hippocampal fissure (up to 6.79%), presubiculum (up to 3.08%), and hippocampal tail (up to −0.23%)). In contrast, no sex differences were detected for the volume of the cornu ammonis (CA)2/3, CA4, Hippocampus-Amygdala Transition Area (HATA), or the granule cell layer of the dentate gyrus (GCDG). These findings show that, independent of differences in HPV, there are regionally specific sex differences in the hippocampus, which may be most prominent in the fimbria and parasubiculum. Further, given sex differences were less consistent across cohorts after controlling for BSV, adjusting for HPV rather than BSV may benefit future studies. This work may help in disentangling sex effects, and provide a better understanding of the implications of sex differences for behaviour and neuropsychiatric disorders.
Published: 2020
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4. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

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

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

Author: Nikita K. Lazaroo, Timothy C. Bates, Narelle K. Hansell, Margaret J. Wright, Nicholas G. Martin, and Michelle Luciano
Subjects: reading ability, scholastic achievement, multivariate modeling, twin design, intelligence, Genetics, QH426-470
Abstract: The aim of this study was to examine whether phonemic decoding skill (deficits of which characterize dyslexia) shares genetic and/or environmental covariance with scholastic abilities independent of general intelligence. Non-word reading ability, verbal and non-verbal IQ, and standardized academic achievement (Queensland Core Skills Test; QCST) were measured in Australian twins (up to 876 twin pairs and 80 singleton twins). Multivariate genetic analysis showed the presence of a general genetic factor, likely reflecting crystallized ability, which accounted for 45–76% of phenotypic variance in QCST scores, 62% of variance in Verbal IQ, 23% of variance in Performance IQ, and 19% of variance in phonological reading ability. The phonemic decoding genetic factor (explaining 48% of variance in phonemic decoding) was negatively associated with mathematical achievement scores (0.4%). Shared effects of common environment did not explain the relationship between reading ability and academic achievement beyond those also influencing IQ. The unique environmental reading factor (accounting for 26% of variance) influenced academic abilities related to written expression. Future research will need to address whether these reading-specific genetic and unique environment relationships arise from causal effects of reading on scholastic abilities, or whether both share a common influence, such as pleiotropic genes/environmental factors.
Published: 2019
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7. Persistence of Anxiety/Depression Symptoms in Early Adolescence: A Prospective Study of Daily Life Stress, Rumination, and Daytime Sleepiness in a Genetically Informative Cohort

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

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

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

9. Robust identification of partial-correlation based networks with applications to cortical thickness data.

Author: David Wheland, Anand A. Joshi, Katie McMahon, Narelle K. Hansell, Nicholas G. Martin, Margaret J. Wright, Paul M. Thompson, David W. Shattuck, and Richard M. Leahy
Published: 2012
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10. Diffusion imaging protocol effects on genetic associations.

Author: Neda Jahanshad, Omid Kohannim, Arthur W. Toga, Katie McMahon, Greig I. de Zubicaray, Narelle K. Hansell, Grant W. Montgomery, Nicholas G. Martin, Margaret J. Wright, and Paul M. Thompson
Published: 2012
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11. Discovery of genes that affect human brain connectivity: A genome-wide analysis of the connectome.

Author: Neda Jahanshad, Derrek P. Hibar, April Ryles, Arthur W. Toga, Katie McMahon, Greig I. de Zubicaray, Narelle K. Hansell, Grant W. Montgomery, Nicholas G. Martin, Margaret J. Wright, and Paul M. Thompson
Published: 2012
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12. Are Sex Differences in Human Brain Structure Associated With Sex Differences in Behavior?

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

13. The Queensland Twin Adolescent Brain Project, a longitudinal study of adolescent brain development

Author: Lachlan T. Strike, Narelle K. Hansell, Kai-Hsiang Chuang, Jessica L. Miller, Greig I. de Zubicaray, Paul M. Thompson, Katie L. McMahon, and Margaret J. Wright
Subjects: Statistics and Probability, Library and Information Sciences, Statistics, Probability and Uncertainty, Computer Science Applications, Education, Information Systems
Abstract: We describe the Queensland Twin Adolescent Brain (QTAB) dataset and provide a detailed methodology and technical validation to facilitate data usage. The QTAB dataset comprises multimodal neuroimaging, as well as cognitive and mental health data collected in adolescent twins over two sessions (session 1: N = 422, age 9–14 years; session 2: N = 304, 10–16 years). The MRI protocol consisted of T1-weighted (MP2RAGE), T2-weighted, FLAIR, high-resolution TSE, SWI, resting-state fMRI, DWI, and ASL scans. Two fMRI tasks were added in session 2: an emotional conflict task and a passive movie-watching task. Outside of the scanner, we assessed cognitive function using standardised tests. We also obtained self-reports of symptoms for anxiety and depression, perceived stress, sleepiness, pubertal development measures, and risk and protective factors. We additionally collected several biological samples for genomic and metagenomic analysis. The QTAB project was established to promote health-related research in adolescence.
Published: 2022

14. Polygenic influences associated with adolescent cognitive skills

Author: Brittany L Mitchell, Narelle K Hansell, Kerrie McAloney, Nicholas G. Martin, Margaret J. Wright, Miguel E. Renteria, and Katrina L. Grasby
Subjects: Arts and Humanities (miscellaneous), Developmental and Educational Psychology, Experimental and Cognitive Psychology
Abstract: Genes play an important role in children’s cognitive ability through puberty and into adolescence. Recent advances in genomics has enabled us to test the effect of various genetic predispositions on measured cognitive outcomes. Here, we leveraged summary statistics from the most recent genome-wide association studies of eleven cognitive and mental health traits to build polygenic prediction models of measured intelligence and academic achievement in a cohort of Australian adolescent twins (N=2,335, 57% female). Additionally, we tested the association of these polygenic risk scores (PRS) with core academic skills such as the ability to comprehend, structure and sequence, evaluate and assess, communicate, and apply techniques and procedures. We show that PRSs for educational attainment, intelligence and cognitive factors explained up to 10% of the variance in educational achievement and 7% in intelligence test scores in our cohort. Additionally, we found that a genetic predisposition for ADHD was negatively associated with all cognitive outcomes and skills and a genetic predisposition for schizophrenia was negatively associated with performance IQ but no other cognitive domain. In this study, we show the potential value of genotypic data for predicting pupil achievement and cognitive developmental trajectory through puberty and into adolescence. We provide evidence that a genetic vulnerability to some mental health disorders is associated with poorer cognitive and educational outcomes, regardless of whether the individual has developed the disorder.
Published: 2022

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

Author: Paul M. Thompson, Brendan P. Zietsch, Greig I. de Zubicaray, Lachlan T. Strike, Katie L. McMahon, Margaret J. Wright, and Narelle K. Hansell
Subjects: Adult, Male, Histology, Biology, 050105 experimental psychology, Young Adult, 03 medical and health sciences, Lateral ventricles, Quantitative Trait, Heritable, 0302 clinical medicine, Genetic variation, Connectome, Twins, Dizygotic, medicine, Humans, 0501 psychology and cognitive sciences, Human Connectome Project, General Neuroscience, 05 social sciences, Brain, Imaging study, Twins, Monozygotic, Human brain, Variance (accounting), Heritability, Genetic architecture, medicine.anatomical_structure, Evolutionary biology, Female, Gene-Environment Interaction, Anatomy, 030217 neurology & neurosurgery
Abstract: Comparing estimates of the amount of genetic and environmental variance for different brain structures may elucidate differences in the genetic architecture or developmental constraints of individual brain structures. However, most studies compare estimates of relative genetic (heritability) and environmental variance in brain structure, which do not reflect differences in absolute variance between brain regions. Here we used a population sample of young adult twins and singleton siblings of twins (n = 791; M = 23 years, Queensland Twin IMaging study) to estimate the absolute genetic and environmental variance, standardised by the phenotypic mean, in the size of cortical, subcortical, and ventricular brain structures. Mean-standardised genetic variance differed widely across structures [23.5-fold range 0.52% (hippocampus) to 12.28% (lateral ventricles)], but the range of estimates within cortical, subcortical, or ventricular structures was more moderate (two to fivefold range). There was no association between mean-standardised and relative measures of genetic variance (i.e., heritability) in brain structure volumes. We found similar results in an independent sample (n = 1075, M = 29 years, Human Connectome Project). These findings open important new lines of enquiry: namely, understanding the bases of these variance patterns, and their implications regarding the genetic architecture, evolution, and development of the human brain.
Published: 2019

16. Are sex differences in human brain structure associated with sex differences in behaviour?

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

17. Genetic and environmental influences on sleep-wake behaviors in adolescence

Author: Jane Burns, Margaret J. Wright, Kerrie McAloney, Haochang Shou, Enda M. Byrne, Nicholas G. Martin, Katie L. McMahon, Joanne S. Carpenter, Victoria S O'Callaghan, Jacob J. Crouse, Kathleen R. Merikangas, Ian B. Hickie, Narelle K. Hansell, Lachlan T. Strike, and Wei Guo
Subjects: Sleep wake, General Medicine, Psychology, Sleep in non-human animals, Sleep duration, Clinical psychology
Abstract: Study Objectives To investigate the influence of genetic and environmental factors on sleep-wake behaviors across adolescence. Methods Four hundred and ninety-five participants (aged 9–17; 55% females), including 93 monozygotic and 117 dizygotic twin pairs, and 75 unmatched twins, wore an accelerometry device and completed a sleep diary for 2 weeks. Results Individual differences in sleep onset, wake time, and sleep midpoint were influenced by both additive genetic (44%–50% of total variance) and shared environmental (31%–42%) factors, with a predominant genetic influence for sleep duration (62%) and restorative sleep (43%). When stratified into younger (aged 9–14) and older (aged 16–17) subsamples, genetic sources were more prominent in older adolescents. The moderate correlation between sleep duration and midpoint (rP = −.43, rG = .54) was attributable to a common genetic source. Sleep-wake behaviors on school and nonschool nights were correlated (rP = .44–.72) and influenced by the same genetic and unique environmental factors. Genetic sources specific to night-type were also identified, for all behaviors except restorative sleep. Conclusions There were strong genetic influences on sleep-wake phenotypes, particularly on sleep timing, in adolescence. Moreover, there may be common genetic influences underlying both sleep and circadian rhythms. The differences in sleep-wake behaviors on school and nonschool nights could be attributable to genetic factors involved in reactivity to environmental context.
Published: 2021

18. Region-specific sex differences in the hippocampus

Author: Paul M. Thompson, Katie L. McMahon, Liza van Eijk, Lachlan T. Strike, Margaret J. Wright, Baptiste Couvy-Duchesne, Brendan P. Zietsch, Narelle K. Hansell, and Greig I. de Zubicaray
Subjects: Adult, Male, Cognitive Neuroscience, Twins, Hippocampus, Physiology, Biology, Hippocampal formation, 050105 experimental psychology, lcsh:RC321-571, Parasubiculum, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Connectome, Brain segmentation, Humans, 0501 psychology and cognitive sciences, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Sex Characteristics, Volume, Dentate gyrus, 05 social sciences, Gender, Organ Size, Magnetic Resonance Imaging, Hippocampal subfields, Neurology, Cohort effect, Hippocampal Fissure, Brain size, Female, Sex, Controlling methods, 030217 neurology & neurosurgery
Abstract: The hippocampus is a brain region critical for learning and memory, and is also implicated in several neuropsychiatric disorders that show sex differences in prevalence, symptom expression, and mean age of onset. On average, males have larger hippocampal volumes than females, but findings are inconclusive after adjusting for overall brain size. Although the hippocampus is a heterogenous structure, few studies have focused on sex differences in the hippocampal subfields – with little consensus on whether there are regionally specific sex differences in the hippocampus after adjusting for brain size, or whether it is important to adjust for total hippocampal volume (HPV). Here, using two young adult cohorts from the Queensland Twin IMaging study (QTIM; N = 727) and the Human Connectome Project (HCP; N = 960), we examined differences between males and females in the volumes of 12 hippocampal subfields, extracted using FreeSurfer 6.0. After adjusting the subfield volumes for either HPV or brain size (brain segmentation volume (BSV)) using four controlling methods (allometric, covariate, residual and matching), we estimated the percentage difference of the sex effect (males versus females) and Cohen's d using hierarchical general linear models. Males had larger volumes compared to females in the parasubiculum (up to 6.04%; Cohen's d = 0.46) and fimbria (up to 8.75%; d = 0.54) after adjusting for HPV. These sex differences were robust across the two cohorts and multiple controlling methods, though within cohort effect sizes were larger for the matched approach, due to the smaller sub-sample. Additional sex effects were identified in the HCP cohort and combined (QTIM and HCP) sample (hippocampal fissure (up to 6.79%), presubiculum (up to 3.08%), and hippocampal tail (up to −0.23%)). In contrast, no sex differences were detected for the volume of the cornu ammonis (CA)2/3, CA4, Hippocampus-Amygdala Transition Area (HATA), or the granule cell layer of the dentate gyrus (GCDG). These findings show that, independent of differences in HPV, there are regionally specific sex differences in the hippocampus, which may be most prominent in the fimbria and parasubiculum. Further, given sex differences were less consistent across cohorts after controlling for BSV, adjusting for HPV rather than BSV may benefit future studies. This work may help in disentangling sex effects, and provide a better understanding of the implications of sex differences for behaviour and neuropsychiatric disorders.
Published: 2020

19. Are there distinct cognitive types?

Author: Nicholas G. Martin, Margaret J. Wright, John C. Loehlin, and Narelle K. Hansell
Subjects: 050103 clinical psychology, education.field_of_study, 05 social sciences, Population, 050301 education, Experimental and Cognitive Psychology, Cognition, Sample (statistics), Cognitive test, Correlation, Arts and Humanities (miscellaneous), Statistics, Replication (statistics), Developmental and Educational Psychology, Cluster (physics), 0501 psychology and cognitive sciences, education, Psychology, Cluster analysis, 0503 education
Abstract: A few previous attempts to isolate cognitive types—groups of individuals with similar profiles of cognitive skills—have been reported in the literature. For the most part, they have not arrived at the same types. The present study sought to identify cognitive types via cluster analysis in an available sample of adolescent twins. Analyses were carried out using one randomly selected twin from each of 16-year-old Australian twin pairs who had taken a five-scale cognitive test battery (N = 677 pairs—a further sample of 628 pairs was reserved for replication purposes). Three levels of tightness of clusters were examined—minimum mutual intercorrelations among cluster members of 0.10, 0.30 and 0.50. The higher intercorrelations led to more clusters—18 at the 0.10 criterion, 25 at 0.30, and 36 at 0.50. The 0.10 level was most similar to the number of clusters reported in previous studies, and was chosen for further analysis. Clustering at this level yielded 18 clusters of individuals from the random twins, and 17 from their co-twins. Fifteen of these matched, as evidenced by a correlation of 0.80 or more between the cluster means. A second method of clustering based on a different approach, SPSS Cluster, gave similar results—15 clusters matched those from the original analysis. Agreement for cluster membership was compared for identical and fraternal twins. A greater agreement for identical twin pairs was found, and interpreted as evidence of a genetic contribution to the clustering. Most of the above analyses were successfully replicated on the reserved sample of twin pairs. Thus there was evidence for stability of initial clustering in this population. However there was not much evidence across studies for discrete and dependable cognitive types.
Published: 2018

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

Author: Dan Rujescu, Vidar M. Steen, Eva Krapohl, Aarno Palotie, Elisabeth Widen, Ingrid Melle, Patrick Sullivan, Katrina L. Grasby, Stephan Ripke, Anke R. Hammerschlag, Christiaan de Leeuw, Panos Bitsios, Nikos C. Stefanis, Tonya White, Gail Davies, Ahmad R. Hariri, Philip R. Jansen, Peter B. Barr, John M. Starr, Max Lam, Ian J. Deary, Sara Hägg, Dimitrios Avramopoulos, Bettina Konte, Anil K. Malhotra, Delilah Zabaneh, Kjetil Sundet, Tinca J. C. Polderman, Ornit Chiba-Falek, Jakob Kaminski, Danielle M. Dick, Andrea Christoforou, Jin Yu, Gunter Schumann, Matthew A. Scult, Anna C. Need, Jens Hjerling-Leffler, Gonçalo R. Abecasis, Kenneth S. Kendler, Todd Lencz, Dwight Dickinson, Bradley T. Webb, Elizabeth T. Cirulli, Stephanie Le Hellard, Gerome Breen, Astri J. Lundervold, Hannah Young, Erin Burke Quinlan, William Ollier, Nikolaos Smyrnis, Emily Drabant Conley, Danielle Posthuma, Sten Linnarsson, Aristotle N. Voineskos, Edythe D. London, Pamela DeRosse, Russell A. Poldrack, Jonathan R. I. Coleman, Jeanne E. Savage, Sarah E. Medland, Ana B. Muñoz-Manchado, Richard E. Straub, Robert Plomin, Ida K. Karlsson, Nathan G. Skene, Dan E. Arking, Birgit Debrabant, Joey W. Trampush, Matthew C. Keller, Mats Nagel, Gary Donohoe, Chandra A. Reynolds, Panos Roussos, Lene Christiansen, Ivar Reinvang, Ole A. Andreassen, Antony Payton, Robert Karlsson, Margaret J. Wright, Deborah C. Koltai, Jari Lahti, Andreas Heinz, Tyrone D. Cannon, Eliza Congdon, Olav B. Smeland, Stella G. Giakoumaki, Marianne Nygaard, Julien Bryois, M. Arfan Ikram, Nancy L. Pedersen, Katri Räikkönen, Daniel R. Weinberger, Neil Pendleton, Swapnil Awasthi, Sven Stringer, Nelson A. Freimer, Aiden Corvin, Kyoko Watanabe, David C. Glahn, Henning Tiemeier, Grant W. Montgomery, Narelle K. Hansell, Robert M. Bilder, Katherine E. Burdick, Srdjan Djurovic, David C. Liewald, Sophie van der Sluis, Thomas Espeseth, Scott I. Vrieze, Fred W. Sabb, Nicholas G. Martin, Michael Gill, Emma Knowles, Derek W. Morris, Alex Hatzimanolis, Ina Giegling, Johan G. Eriksson, Child and Adolescent Psychiatry / Psychology, Epidemiology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Biological Psychology, Functional Genomics, Research Programs Unit, Diabetes and Obesity Research Program, Department of General Practice and Primary Health Care, Johan Eriksson / Principal Investigator, Clinicum, University of Helsinki, Medicum, Helsinki Collegium for Advanced Studies, Department of Psychology and Logopedics, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Elisabeth Ingrid Maria Widen / Principal Investigator, Developmental Psychology Research Group, Genomics of Neurological and Neuropsychiatric Disorders, Genomic Discoveries and Clinical Translation, Human genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, VU University medical center, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Amsterdam Reproduction & Development (AR&D)
Subjects: 0301 basic medicine, Nonsynonymous substitution, Male, GENERAL COGNITIVE FUNCTION, Intelligence, LOCI, Genome-wide association study, ANNOTATION, 0302 clinical medicine, GWAS, 11 Medical and Health Sciences, Genetics & Heredity, RISK, HERITABILITY, Brain, Mendelian Randomization Analysis, Middle Aged, 3. Good health, Schizophrenia, Genome-Wide Association Study/methods, Female, Life Sciences & Biomedicine, TRAITS, Adolescent, Quantitative Trait Loci, Computational biology, Biology, Quantitative trait locus, Brain/physiology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Genetics, medicine, Humans, Genetic Predisposition to Disease, Gene, Genetic association, EDUCATIONAL-ATTAINMENT, Science & Technology, TEST BATTERIES, CONSORTIUM, Intelligence/genetics, 06 Biological Sciences, medicine.disease, 030104 developmental biology, Expression quantitative trait loci, 3111 Biomedicine, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract: Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7 , but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Published: 2018

21. Genome‐wide association analysis links multiple psychiatric liability genes to oscillatory brain activity

Author: Damiaan Denys, Jian Zhang, Paul M. Thompson, Eco J. C. de Geus, Stephen M. Malone, Jacquelyn L. Meyers, Neda Jahanshad, Jouke-Jan Hottenga, Nicholas G. Martin, David B. Chorlian, Bernice Porjesz, Narelle K. Hansell, Sarah E. Medland, Dirk J.A. Smit, William G. Iacono, Margaret J. Wright, Yvonne Y.W. Ho, Catharina E.M. van Beijsterveldt, Scott J. Burwell, Matt McGue, Christopher D. Whelan, Dorret I. Boomsma, Adult Psychiatry, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Brain Imaging, Biological Psychology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, and APH - Methodology
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Male, Periodicity, brain expression pathway, Brain activity and meditation, Gene Expression, Genome-wide association study, Electroencephalography, Hippocampal formation, Cohort Studies, 0302 clinical medicine, electroencephalography (EEG), Child, Research Articles, Genetics, 0303 health sciences, Radiological and Ultrasound Technology, biology, medicine.diagnostic_test, Mental Disorders, Brain, Middle Aged, genetic correlation, endophenotype, Neurology, Child, Preschool, Female, Anatomy, Research Article, Adult, Adolescent, Rest, Single-nucleotide polymorphism, Quantitative trait locus, Genome‐Wide Association Study (GWAS), Polymorphism, Single Nucleotide, SNP heritability, 03 medical and health sciences, Young Adult, SDG 3 - Good Health and Well-being, medicine, SNP, Humans, Radiology, Nuclear Medicine and imaging, GABRA2, Genetic Predisposition to Disease, Bipolar disorder, 030304 developmental biology, Aged, Genome-Wide Association Study (GWAS), medicine.disease, 030104 developmental biology, Endophenotype, Expression quantitative trait loci, biology.protein, Neurology (clinical), Neuroscience, Imputation (genetics), 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Oscillatory activity is crucial for information processing in the brain, and has a long history as a biomarker for psychopathology. Variation in oscillatory activity is highly heritable, but the involvement of specific genetic variants, genes, and brain expression pathways remains elusive. Here, we present a genome-wide association study (GWAS) for the power of oscillations at standard frequencies (~2 Hz delta, ~6 Hz theta, ~10 Hz alpha, and ~20 Hz beta) of the electroencephalogram (EEG), followed up with gene-based and brain-expression analyses based on the extraction of RNA expression quantitative trait loci (eQTL) and imputation of gene expression in brain tissues by machine learning (Metaxcan). Five cohorts with eyes-closed resting EEG and genome-wide single nucleotide polymorphism (SNP) were included with data for 8425 participants. GWAS revealed a significant SNP for alpha oscillation power intronic to protein-coding gene PRKG2. PRKG2 is amongst the genes deleted in the 4q21 microdeletion syndrome which results in speech and mental retardation. GABRA2 -- a known genetic marker for alcohol use disorder and epilepsy -- significantly affected beta power, consistent with the relation between GABAA interneuron activity and beta oscillations, and between beta oscillations and alcohol use disorders. Twenty-four genes in region 3p21.1 -- previously linked to schizophrenia -- reached significance for alpha power, which fits well with observed aberrant oscillatory activity in schizophrenia. SNPs in this region were eQTLs for GLYCTK in hippocampal tissue, and eQTLs for GNL3 and ITIH4 in the frontal cortex. SNP-based imputation of hippocampal GABRA2 expression was significantly associated with beta oscillations and indicated associations of immune genes IL18R1 and IL1RL1 in the Hippocampus and Putamen with alpha oscillation strength. In conclusion, we successfully associated genes and genetic variants with oscillatory brain activity, some of which were previously associated with psychopathology. The results show how psychopathological liability genes affect brain functioning via cortical and subcortical brain expression.
Published: 2018

22. The Nature of Nurture: Using a Virtual-Parent Design to Test Parenting Effects on Children's Educational Attainment in Genotyped Families

Author: Kenneth S. Kendler, Nicholas G. Martin, Narelle K. Hansell, Sarah E. Medland, Nathan A. Gillespie, Brion S. Maher, Timothy C. Bates, Margaret J. Wright, and Kerrie McAloney
Subjects: Male, 0301 basic medicine, virtual-parent design, Adolescent, Genotype, Offspring, non-transmitted genotype, Twins, Polymorphism, Single Nucleotide, Structural equation modeling, Nature versus nurture, Education, 03 medical and health sciences, 0302 clinical medicine, Humans, Allele, Alleles, Genetics (clinical), parental environment, Parenting, Obstetrics and Gynecology, Causality, Confidence interval, Educational attainment, 030104 developmental biology, educational attainment, Pediatrics, Perinatology and Child Health, Female, Gene-Environment Interaction, Social competence, Psychology, 030217 neurology & neurosurgery, Genome-Wide Association Study, Demography
Abstract: Research on environmental and genetic pathways to complex traits such as educational attainment (EA) is confounded by uncertainty over whether correlations reflect effects of transmitted parental genes, causal family environments, or some, possibly interactive, mixture of both. Thus, an aggregate of thousands of alleles associated with EA (a polygenic risk score; PRS) may tap parental behaviors and home environments promoting EA in the offspring. New methods for unpicking and determining these causal pathways are required. Here, we utilize the fact that parents pass, at random, 50% of their genome to a given offspring to create independent scores for the transmitted alleles (conventional EA PRS) and a parental score based on allelesnot transmittedto the offspring (EA VP_PRS). The formal effect of non-transmitted alleles on offspring attainment was tested in 2,333 genotyped twins for whom high-quality measures of EA, assessed at age 17 years, were available, and whose parents were also genotyped. Four key findings were observed. First, the EA PRS and EA VP_PRS were empirically independent, validating the virtual-parent design. Second, in this family-based design, children's own EA PRS significantly predicted their EA (β = 0.15), ruling out stratification confounds as a cause of the association of attainment with the EA PRS. Third, parental EA PRS predicted the SES environment parents provided to offspring (β = 0.20), and parental SES and offspring EA were significantly associated (β = 0.33). This would suggest that the EA PRS is at least as strongly linked to social competence as it is to EA, leading to higher attained SES in parents and, therefore, a higher experienced SES for children. In a full structural equation model taking account of family genetic relatedness across multiple siblings the non-transmitted allele effects were estimated at similar values; but, in this more complex model, confidence intervals included zero. A test using the forthcoming EA3 PRS may clarify this outcome. The virtual-parent method may be applied to clarify causality in other phenotypes where observational evidence suggests parenting may moderate expression of other outcomes, for instance in psychiatry.
Published: 2018

23. Social Competence in Parents Increases Children’s Educational Attainment: Replicable Genetically-Mediated Effects of Parenting Revealed by Non-Transmitted DNA

Author: Lucía Colodro-Conde, Aysu Okbay, Kenneth S. Kendler, Brion S. Maher, Nicholas G. Martin, Timothy C. Bates, Margaret J. Wright, Sarah E. Medland, Kerrie McAloney, Nathan A. Gillespie, Narelle K. Hansell, Economics, and Amsterdam Neuroscience - Complex Trait Genetics
Subjects: Male, 0301 basic medicine, virtual-parent design, Adolescent, Offspring, socio-economic status, non-transmitted genotype, Twins, Genome-wide association study, PRS, socioeconomic status, 03 medical and health sciences, 0302 clinical medicine, parenting, Humans, Medicine, Allele, Socioeconomic status, Genetics (clinical), Genetic association, parental environment, business.industry, Obstetrics and Gynecology, Educational attainment, polygenic risk scores, 030104 developmental biology, Socioeconomic Factors, educational attainment, Pediatrics, Perinatology and Child Health, Educational Status, Female, Polygenic risk score, Social competence, SES, business, SDG 4 - Quality Education, 030217 neurology & neurosurgery, Genome-Wide Association Study, Demography
Abstract: We recently reported an association of offspring educational attainment with polygenic risk scores (PRS) computed on parent’s non-transmitted alleles for educational attainment using the second GWAS meta-analysis article on educational attainment published by the Social Science Genetic Association Consortium. Here we test the replication of these findings using a more powerful PRS from the third GWAS meta-analysis article by the Consortium. Each of the key findings of our previous paper is replicated using this improved PRS (N = 2335 adolescent twins and their genotyped parents). The association of children’s attainment with their own PRS increased substantially with the standardized effect size, moving from β = 0.134, 95% CI = 0.079, 0.188 for EA2, to β = 0.223, 95% CI = 0.169, 0.278, p < .001, for EA3. Parent’s PRS again predicted the socioeconomic status (SES) they provided to their offspring and increased from β = 0.201, 95% CI = 0.147, 0.256 to β = 0.286, 95% CI = 0.239, 0.333. Importantly, the PRS for alleles not transmitted to their offspring — therefore acting via the parenting environment — was increased in effect size from β = 0.058, 95% CI = 0.003, 0.114 to β = 0.067, 95% CI = 0.012, 0.122, p = .016. As previously found, this non-transmitted genetic effect was fully accounted for by parental SES. The findings reinforce the conclusion that genetic effects of parenting are substantial, explain approximately one-third the magnitude of an individual’s own genetic inheritance and are mediated by parental socioeconomic competence.
Published: 2019

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

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

25. Genetic influences on individual differences in longitudinal changes in global and subcortical brain volumes: Results of the ENIGMA plasticity working group

Author: Nicholas G. Martin, Matthew S. Panizzon, Karen A. Mather, William S. Kremen, Ian B. Hickie, Anbupalam Thalamuthu, David C. Glahn, Wei Wen, Xue Hua, Narelle K. Hansell, Marinka M.G. Koenis, Lucija Abramovic, Dorret I. Boomsma, Carol E. Franz, Suzanne C. Swagerman, Greig I. de Zubicaray, Rachel M. Brouwer, René S. Kahn, John H. Gilmore, Hugo G. Schnack, Margaret J. Wright, Perminder S. Sachdev, Neda Jahanshad, Hilleke E. Hulshoff Pol, Derrek P. Hibar, Katie L. McMahon, Nitin Gogtay, Paul M. Thompson, and Lachlan T. Strike
Subjects: Cerebellum, Radiological and Ultrasound Technology, 05 social sciences, Thalamus, Heritability, 050105 experimental psychology, 03 medical and health sciences, Lateral ventricles, 0302 clinical medicine, medicine.anatomical_structure, Neurology, Ageing, Neuroplasticity, Brain size, medicine, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, sense organs, Neurology (clinical), Cognitive skill, Anatomy, skin and connective tissue diseases, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract: Structural brain changes that occur during development and ageing are related to mental health and general cognitive functioning. Individuals differ in the extent to which their brain volumes change over time, but whether these differences can be attributed to differences in their genotypes has not been widely studied. Here we estimate heritability (h2) of changes in global and subcortical brain volumes in five longitudinal twin cohorts from across the world and in different stages of the lifespan (N = 861). Heritability estimates of brain changes were significant and ranged from 16% (caudate) to 42% (cerebellar gray matter) for all global and most subcortical volumes (with the exception of thalamus and pallidum). Heritability estimates of change rates were generally higher in adults than in children suggesting an increasing influence of genetic factors explaining individual differences in brain structural changes with age. In children, environmental influences in part explained individual differences in developmental changes in brain structure. Multivariate genetic modeling showed that genetic influences of change rates and baseline volume significantly overlapped for many structures. The genetic influences explaining individual differences in the change rate for cerebellum, cerebellar gray matter and lateral ventricles were independent of the genetic influences explaining differences in their baseline volumes. These results imply the existence of genetic variants that are specific for brain plasticity, rather than brain volume itself. Identifying these genes may increase our understanding of brain development and ageing and possibly have implications for diseases that are characterized by deviant developmental trajectories of brain structure.
Published: 2017

26. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Peter W. Schofield, Dan Rujescu, Gail Davies, Vidar M. Steen, Ahmad R. Hariri, Sara Hägg, Lars Nyberg, Dimitrios Avramopoulos, Nikolaos Smyrnis, Gerardo Heiss, Pamela DeRosse, Russell A. Poldrack, Jingyun Yang, Evangelos Evangelou, Katri Räikkönen, Fred W. Sabb, B. Gwen Windham, Aiden Corvin, Peter R. Schofield, Teemu Palviainen, André G. Uitterlinden, Anders Lundquist, Henry Brodaty, Aarno Palotie, Gary Donohoe, Elisabeth Widen, Teresa Lee, Cornelia M. van Duijn, Harry Campbell, Caroline Hayward, Rebecca F. Gottesman, Shuo Li, Steffi G. Riedel-Heller, M. Arfan Ikram, Sudha Seshadri, Jari Lahti, Joshua C. Bis, Panos Bitsios, Nikos C. Stefanis, Bettina Konte, Steven T. Turner, Edith Hofer, Vilmundur Gudnason, Michael Gill, P. Eline Slagboom, Ozren Polasek, Ida K. Karlsson, Christopher Oldmeadow, Michael Griswold, Ulman Lindenberger, Eric Boerwinkle, Saskia P. Hagenaars, Ingrid Melle, Alfredo Ramirez, Janie Corley, Rodney J. Scott, Sven J. van der Lee, Mika Kähönen, Alison D. Murray, Daniel R. Weinberger, Neil Pendleton, J. Wouter Jukema, Suvi P. Rovio, Wei Zhao, Muralidharan Sargurupremraj, Raha Pazoki, Matthias Schmid, Ina Giegling, Grant W. Montgomery, Daniel E. Gustavson, Jerome I. Rotter, Dan E. Arking, Oscar L. Lopez, David J. Stott, Julian N. Trollor, Chandra A. Reynolds, Tobias Luck, Andrea Christoforou, David J. Porteous, Kent D. Taylor, Simon R. Cox, Yasaman Saba, Matthew A. Scult, Astri J. Lundervold, Aicha Soumare, Antony Payton, Stella Trompet, W. David Hill, Shu-Chen Li, Robert M. Bilder, Eero Vuoksimaa, Jennifer A. Smith, Katherine E. Burdick, Deborah K. Attix, Sudheer Giddaluru, David C. Glahn, Edythe D. London, Stephanie Le Hellard, Terho Lehtimäki, Markus Leber, Katja Petrovic, James F. Wilson, Dwight Dickinson, Elizabeth T. Cirulli, Christophe Tzourio, Panos Roussos, Amelia A. Assareh, Markus Scholz, Alex Hatzimanolis, Tamara B. Harris, Stéphanie Debette, Alison Pattie, Thomas Espeseth, John M. Starr, William E R Ollier, Nicola J. Armstrong, Kjetil Sundet, Michael Wagner, Ian Ford, Simone Reppermund, Qiong Yang, Albert V. Smith, Nicole A. Kochan, Riccardo E. Marioni, Anu Loukola, Igor Rudan, Nicholas G. Martin, Jan Bressler, Tian Liu, K. Hoyan Wen, Natalie Terzikhan, Emma Knowles, Raymond Noordam, Joey W. Trampush, John Attia, Nancy L. Pedersen, Claudia L. Satizabal, Anne C. Böhmer, Chloe Fawns-Ritchie, Adele M. Taylor, Bruce M. Psaty, Paul Elliott, David R. Weir, Catharine R. Gale, Ioanna Tzoulaki, Leonie Weinhold, Anbupalam Thalamuthu, Anders M. Dale, Helena Schmidt, Annette M. Hartmann, Ole A. Andreassen, Ian J. Deary, Arno Villringer, Andrew M. McIntosh, Srdjan Djurovic, Najaf Amin, David C. Liewald, Nathan A. Gillespie, Ivar Reinvang, Thomas H. Mosley, Veronique Vitart, Michelle Luciano, Robert Karlsson, Lenore J. Launer, Eliza Congdon, Karen A. Mather, Marisa Koini, Tyrone D. Cannon, Elizabeth G. Holliday, Goran Papenberg, Reinhold Schmidt, Philippe Amouyel, Holger Wagner, Todd Lencz, Margaret J. Wright, Leo-Pekka Lyytikäinen, Emily Drabant Conley, David A. Bennett, William S. Kremen, M. Kamran Ikram, Catriona L. K. Barnes, Stella G. Giakoumaki, Scott D. Gordon, Johan G. Eriksson, Perminder S. Sachdev, Olli T. Raitakari, Judith A. Okely, Aristotle N. Voineskos, Max Lam, Sarah E. Harris, Luca Kleineidam, Jaakko Kaprio, Derek W. Morris, Sharon L.R. Kardia, Peter K. Joshi, Erin B. Ware, Lars Bertram, Philip L. De Jager, Anna C. Need, Abbas Dehghan, Jin Yu, Jessica D. Faul, N Freimer, Matthew C. Keller, John B.J. Kwok, Anil K. Malhotra, Will Longstreth, Hieab H.H. Adams, Richard J. Rose, Annette L. Fitzpatrick, Richard E. Straub, Christina M. Lill, David Ames, Patricia A. Boyle, David S. Knopman, He Gao, Narelle K. Hansell, Ornit Chiba-Falek, Danielle M. Dick, Stuart J. Ritchie, Ari Ahola-Olli, and Jeannette Simino
Subjects: 0301 basic medicine, Science, MEDLINE, General Physics and Astronomy, 02 engineering and technology, computer.software_genre, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, lcsh:Science, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Multidisciplinary, business.industry, Published Erratum, Cognition, General Chemistry, 021001 nanoscience & nanotechnology, 030104 developmental biology, Correction study, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, lcsh:Q, Artificial intelligence, ddc:500, 0210 nano-technology, Psychology, business, computer, Natural language processing
Abstract: Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.
Published: 2019

27. Genetic and environmental contributions to cognitive structure in Australian twins: A reappraisal

Author: Nicholas G. Martin, John C. Loehlin, Narelle K. Hansell, and Margaret J. Wright
Subjects: Arts and Humanities (miscellaneous), 05 social sciences, Developmental and Educational Psychology, 050109 social psychology, 0501 psychology and cognitive sciences, Experimental and Cognitive Psychology, Cognitive structure, Psychology, 050105 experimental psychology, Cognitive psychology
Published: 2016

28. Abstracts From the ISTS Satellite Meeting June 20, 2016, Brisbane

Author: Gabriel Cuellar-Partida, Margaret J. Wright, Trung Thanh Ngo, Scott D. Gordon, Nicholas G. Martin, Steven M. Miller, Narelle K. Hansell, P. C. F. Law, Baptiste Couvy-Duchesne, Miguel E. Rentería, L. Colodro Conde, and S. E. Medland
Subjects: Binocular rivalry, medicine.medical_specialty, Anxiety depression, Obstetrics and Gynecology, medicine.disease, Endophenotype, Pediatrics, Perinatology and Child Health, medicine, Major depressive disorder, Bipolar disorder, Association (psychology), Psychology, Psychiatry, Genetics (clinical), Clinical psychology
Published: 2016

29. When does socioeconomic status (SES) moderate the heritability of IQ? No evidence for g × SES interaction for IQ in a representative sample of 1176 Australian adolescent twin pairs

Author: Nicholas G. Martin, Narelle K. Hansell, Margaret J. Wright, and Timothy C. Bates
Subjects: child development, Bioecological model, Intelligence quotient, 05 social sciences, 050109 social psychology, Experimental and Cognitive Psychology, Cognition, Child development, 050105 experimental psychology, Developmental psychology, Arts and Humanities (miscellaneous), IQ, Heritability of IQ, Developmental and Educational Psychology, Cognitive development, 0501 psychology and cognitive sciences, G × SES, Gene–environment interaction, gene–environment interaction, Psychology, Socioeconomic status, cognitive development
Abstract: Bioecological theory predicts that cognitive ability is more heritable among those raised in higher socioeconomic status (SES) families. However, the mechanism of this effect is unclear, and the effect may not be universal. We tested for gene × SES interaction effects on Full-scale IQ in 2,307 adolescent Australian twins (mean age 16.2 years). Mean IQ scores were modestly higher among those from higher SES backgrounds, but the magnitude of genetic influences on IQ was uniformly high across the range of SES. Research identifying the conditions under which expressed genetic potential can become decoupled from parental SES, as seen here, is needed. We speculate that school provision may be key.
Published: 2016

30. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author: Robert F. Krueger, Teresa Nutile, Georg Homuth, Ina Giegling, Aarno Palotie, Katja Appel, Grant W. Montgomery, Elisabeth Widen, Jouke-Jan Hottenga, Beate St Pourcain, Caroline Hayward, Andrea Maschio, Andrew C. Heath, Narelle K. Hansell, Terho Lehtimäki, Wendy S. Slutske, Sarah E. Medland, Johan G. Eriksson, John M. Starr, Antonio Terracciano, Jonathan Marten, Olli T. Raitakari, Liisa Keltikangas-Järvinen, Igor Rudan, Kati Heinonen, Brenda W.J.H. Penninx, David J. Porteous, Klaasjan G. Ouwens, Barbara Franke, Jaakko Kaprio, Erik Pettersson, Jueri Allik, Ian J. Deary, Alessandra Minelli, Nicholas G. Martin, William G. Iacono, Yuri Milaneschi, Ilkka Seppälä, David M. Evans, Lina Zgaga, John P. Kemp, Alexander Teumer, Dorret I. Boomsma, Harry Campbell, Margaret J. Wright, Abraham A. Palmer, Jun Ding, Patrik K. E. Magnusson, Marleen H. M. de Moor, James F. Wilson, Anu Realo, Paul T. Costa, Scott D. Gordon, Jaime Derringer, Michel G. Nivard, Cornelia M. van Duijn, David C. Liewald, David Schlessinger, Marina Ciullo, Juho Wedenoja, Amy B. Hart, Laura J. Bierut, Angelina R. Sutin, Hamdi Mbarek, Alexander Viktorin, Stéphanie Martine van den Berg, Ozren Polasek, Harriet de Wit, Jari Lahti, Dan Rujescu, Nicholas J. Timpson, Matthias Nauck, Fabio Busonero, Iryna O. Fedko, Evelin Mihailov, Gonçalo R. Abecasis, John M. Hettema, Daniel E. Adkins, Hans J. Grabe, Richard A. Grucza, Luigi Ferrucci, Alejandro Arias Vasquez, Barbara E. Engelhardt, Laura Pulkki-Råback, Antti Latvala, Bettina Konte, Michelle Luciano, Robert Karlsson, Chiara Magri, Sita H. Vermeulen, Tõnu Esko, Arpana Agrawal, Matt McGue, Holly Trochet, Joost G. E. Janzing, Gail Davies, Toshiko Tanaka, Rossella Sorice, Timothy B. Bigdeli, Abdel Abdellaoui, Karin J. H. Verweij, Andres Metspalu, Nancy L. Pedersen, Anjali K. Henders, Matthew G. Kirkpatrick, Yong Qian, Lindsay K. Matteson, Annette M. Hartmann, George Davey Smith, Michael B. Miller, Najaf Amin, Pamela A. F. Madden, Richard J. Rose, Minyoung Lee, Eero Vuoksimaa, Katri Räikkönen, Markus Jokela, Jennifer E. Huffman, Carsten Oliver Schmidt, Jasper Wouda, Daniela Ruggiero, Academic Medical Center, Helsinki Collegium for Advanced Studies, Behavioural Sciences, Clinicum, Department of Public Health, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Diabetes and Obesity Research Program, Research Programs Unit, Institute for Molecular Medicine Finland, Aarno Palotie / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Jaakko Kaprio / Principal Investigator, Psychosocial factors and health, Developmental Psychology Research Group, Genomics of Neurological and Neuropsychiatric Disorders, Genetic Epidemiology, Genomic Discoveries and Clinical Translation, Faculty of Behavioural, Management and Social Sciences, Psychiatry, EMGO - Mental health, Amsterdam Neuroscience - Complex Trait Genetics, IOO, EMGO+ - Mental Health, Biological Psychology, Clinical Child and Family Studies, Erasmus MC other, and Epidemiology
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Multifactorial Inheritance, Genome-wide association study, Cohort Studies, Extraversion, Psychological, 0302 clinical medicine, Risk Factors, NEUROTICISM, Genetics(clinical), IR-99241, Big Five personality traits, Genetics (clinical), Original Research, media_common, Genetics, Ecology, HERITABILITY, METIS-315471, Polymorphism, Single Nucleotide/genetics, Neuroticism, 3142 Public health care science, environmental and occupational health, Common genetic variants, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Trait, Psychology, Personality, DIMENSIONS, NEUROTROPHIC FACTOR BDNF, Evolution, 515 Psychology, media_common.quotation_subject, Single-nucleotide polymorphism, Phenotype harmonization, Polymorphism, Single Nucleotide, Imputation, Polygenic risk, Ecology, Evolution, Behavior and Systematics, 03 medical and health sciences, Behavior and Systematics, Personality/genetics, CLONINGERS TEMPERAMENT SCALES, 5-FACTOR MODEL, Humans, Multifactorial Inheritance/genetics, PSYCHOBIOLOGICAL MODEL, Extraversion and introversion, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Other Research Radboud Institute for Health Sciences [Radboudumc 0], Extraversion (Psychology), COMMON SNPS EXPLAIN, 030104 developmental biology, LARGE PROPORTION, 3111 Biomedicine, Developmental Psychopathology, HUMAN HEIGHT, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion. © 2015, The Author(s). Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
Published: 2016

31. Genetic Complexity of Cortical Structure: Differences in Genetic and Environmental Factors Influencing Cortical Surface Area and Thickness

Author: Katie L. McMahon, Lachlan T. Strike, Paul M. Thompson, Greig I. de Zubicaray, Margaret J. Wright, Narelle K. Hansell, and Baptiste Couvy-Duchesne
Subjects: Adult, Male, Adolescent, Cognitive Neuroscience, Biology, 050105 experimental psychology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, 0302 clinical medicine, medicine, Connectome, Humans, 0501 psychology and cognitive sciences, Gene–environment interaction, Cerebral Cortex, Human Connectome Project, 05 social sciences, Original Articles, Heritability, Twin study, Magnetic Resonance Imaging, Genetic architecture, medicine.anatomical_structure, Cerebral cortex, Evolutionary biology, Female, Gene-Environment Interaction, Occipital lobe, 030217 neurology & neurosurgery
Abstract: Quantifying the genetic architecture of the cerebral cortex is necessary for understanding disease and changes to the brain across the lifespan. Prior work shows that both surface area (SA) and cortical thickness (CT) are heritable. However, we do not yet understand the extent to which region-specific genetic factors (i.e., independent of global effects) play a dominant role in the regional patterning or inter-regional associations across the cortex. Using a population sample of young adult twins (N = 923), we show that the heritability of SA and CT varies widely across regions, generally independent of measurement error. When global effects are controlled for, we detected a complex pattern of genetically mediated clusters of inter-regional associations, which varied between hemispheres. There were generally weak associations between the SA of different regions, except within the occipital lobe, whereas CT was positively correlated within lobar divisions and negatively correlated across lobes, mostly due to genetic covariation. These findings were replicated in an independent sample of twins and siblings (N = 698) from the Human Connectome Project. The different genetic contributions to SA and CT across regions reveal the value of quantifying sources of covariation to appreciate the genetic complexity of cortical structures.
Published: 2018

32. Heritability of the network architecture of intrinsic brain functional connectivity

Author: Nicholas G. Martin, Katie L. McMahon, Gabriëlla A.M. Blokland, Margaret J. Wright, Benjamin Sinclair, Narelle K. Hansell, Michael Breakspear, Greig I. de Zubicaray, and Paul M. Thompson
Subjects: Adult, Male, Adolescent, Resting state fMRI, Cognitive Neuroscience, Brain, Graph theory, Heritability, Article, Regression, Combinatorics, Young Adult, Neurology, Endophenotype, Statistics, Connectome, Humans, Graph (abstract data type), Female, Genetic Phenomena, Nerve Net, Genetic association, Mathematics, Clustering coefficient
Abstract: The brain's functional network exhibits many features facilitating functional specialization, integration, and robustness to attack. Using graph theory to characterize brain networks, studies demonstrate their small-world, modular, and "rich-club" properties, with deviations reported in many common neuropathological conditions. Here we estimate the heritability of five widely used graph theoretical metrics (mean clustering coefficient (γ), modularity (Q), rich-club coefficient (ϕnorm), global efficiency (λ), small-worldness (σ)) over a range of connection densities (k=5-25%) in a large cohort of twins (N=592, 84 MZ and 89 DZ twin pairs, 246 single twins, age 23 ± 2.5). We also considered the effects of global signal regression (GSR). We found that the graph metrics were moderately influenced by genetic factors h(2) (γ=47-59%, Q=38-59%, ϕnorm=0-29%, λ=52-64%, σ=51-59%) at lower connection densities (≤ 15%), and when global signal regression was implemented, heritability estimates decreased substantially h(2) (γ=0-26%, Q=0-28%, ϕnorm=0%, λ=23-30%, σ=0-27%). Distinct network features were phenotypically correlated (|r|=0.15-0.81), and γ, Q, and λ were found to be influenced by overlapping genetic factors. Our findings suggest that these metrics may be potential endophenotypes for psychiatric disease and suitable for genetic association studies, but that genetic effects must be interpreted with respect to methodological choices.
Published: 2015

33. Low Birth Weight in MZ Twins Discordant for Birth Weight is Associated with Shorter Telomere Length and lower IQ, but not Anxiety/Depression in Later Life

Author: Marcella Rietschel, Nicholas G. Martin, Veryan Codd, Gonneke Willemsen, Ian B. Hickie, Jana Strohmaier, Richard Saffery, Nilesh J. Samani, Jenny van Dongen, Anjali K. Henders, Dale R. Nyholt, Narelle K. Hansell, Margaret J. Wright, Grant W. Montgomery, Fabian Streit, Nathan A. Gillespie, Liz Rietschel, Jeffrey M. Craig, Boris Novakovic, Gu Zhu, Dorret I. Boomsma, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, and EMGO+ - Mental Health
Subjects: Male, Netherlands Twin Register (NTR), medicine.medical_specialty, Adolescent, Birth weight, Intelligence, Anxiety depression, Population, Anxiety, Telomere Homeostasis, Internal medicine, Twins, Dizygotic, medicine, Humans, Longitudinal Studies, Child, education, Genetics (clinical), Genetics, education.field_of_study, Intelligence quotient, Depression, Infant, Newborn, Infant, Obstetrics and Gynecology, Twins, Monozygotic, Infant, Low Birth Weight, Telomere, Low birth weight, Endocrinology, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, Psychology
Abstract: Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.
Published: 2015

34. Genetics and Brain Morphology

Author: Baptiste Couvy-Duchesne, Margaret J. Wright, Gabriel Cuellar-Partida, Sarah E. Medland, Narelle K. Hansell, and Lachlan T. Strike
Subjects: Candidate gene, Brain morphometry, Brain, Genetic Variation, Neuroimaging, Genome-wide association study, Heritability, Twin study, Genetic architecture, Cognition, Phenotype, Neuropsychology and Physiological Psychology, Evolutionary biology, Genetic variation, Humans, Twin Studies as Topic, Psychology, Genome-Wide Association Study, Genetic association
Abstract: A wealth of empirical evidence is accumulating on the genetic mediation of brain structure phenotypes. This comes from twin studies that assess heritability and genetic covariance between traits, candidate gene associations, and genome-wide association studies (GWAS) that can identify specific genetic variants. Here we review the major findings from each of these approaches and consider how they inform on the genetic architecture of brain structure. The findings from twin studies show there is a strong genetic influence (heritability) on brain structure, and overlap of genetic effects (pleiotropy) between structures, and between structure and cognition. However, there is also evidence for genetic specificity, with distinct genetic effects across some brain regions. Candidate gene associations show little convergence; most have been under powered to detect effect sizes of the magnitude now expected. GWAS have identified 19 genetic variants for brain structure, though no replicated associations account for more than 1 % of the variance. Together these studies are revealing new insights into the genetic architecture of brain morphology. As the scope of inquiry broadens, including measures that capture the complexity of the brain, along with larger samples and new analyses, such as genome-wide common trait analysis (GCTA) and polygenic scores, which combine variant effects for a phenotype, as well as whole-genome sequencing, more genetic variants for brain structure will be identified. Increasingly, large-scale multi-site studies will facilitate this next wave of studies, and promise to enhance our understanding of the etiology of variation in brain morphology, as well as brain disorders.
Published: 2015

35. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder

Author: Igor Rudan, Barbara Franke, Margaret J. Wright, Juho Wedenoja, Laura J. Bierut, Anjali K. Henders, Teresa Nutile, Andrew C. Heath, Joost G. E. Janzing, Anu Realo, Ilkka Seppälä, Lindsay K. Matteson, Nicholas J. Timpson, Tõnu Esko, Arpana Agrawal, Abraham A. Palmer, Rossella Sorice, Andres Metspalu, Patrik K. E. Magnusson, Aarno Palotie, Katja Appel, Elisabeth Widen, Ozren Polasek, Katri Räikkönen, Marleen H. M. de Moor, Matthew G. Kirkpatrick, Caroline Hayward, Hans Joergen Grabe, Ian J. Deary, Nicholas G. Martin, Karin J. H. Verweij, Klaasjan G. Ouwens, Alessandra Minelli, Angelina R. Sutin, William G. Iacono, Jennifer E. Huffman, Marina Ciullo, Dorret I. Boomsma, Harry Campbell, N. L. Pedersen, David J. Porteous, Timothy B. Bigdeli, Jasper Wouda, Jun Ding, Alexander Viktorin, David C. Liewald, Gonçalo R. Abecasis, Richard A. Grucza, Carsten Oliver Schmidt, Antti Latvala, James F. Wilson, Luigi Ferrucci, Erik Pettersson, Beate St Pourcain, Scott D. Gordon, Grant W. Montgomery, Stéphanie Martine van den Berg, Jaime Derringer, Yuri Milaneschi, Alexander Teumer, Holly Trochet, Daniel E. Adkins, Jaakko Kaprio, Brenda W.J.H. Penninx, Chiara Magri, Sita H. Vermeulen, Terho Lehtimäki, Alejandro Arias Vasquez, Harriet de Wit, Jari Lahti, Jouke-Jan Hottenga, Matt McGue, Johan G. Eriksson, Daniela Ruggiero, John P. Kemp, Toshiko Tanaka, Iryna O. Fedko, Jüri Allik, Yong Qian, Annette M. Hartmann, Cornelia M. van Duijn, Barbara E. Engelhardt, Laura Pulkki-Råback, Jonathan Marten, Pamela A. F. Madden, Olli T. Raitakari, Michelle Luciano, Robert Karlsson, Amy B. Hart, Gail Davies, Liisa Keltikangas-Järvinen, Robert F. Krueger, Narelle K. Hansell, Kati Heinonen, Georg Homuth, Eero Vuoksimaa, Wendy S. Slutske, Sarah E. Medland, Andrea Maschio, Najaf Amin, John M. Starr, Antonio Terracciano, David M. Evans, Markus Jokela, Lina Zgaga, Dan Rujescu, David Schlessinger, Ina Giegling, Matthias Nauck, John M. Hettema, Evelin Mihailov, Paul T. Costa, Michael B. Miller, Bettina Konte, Minyoung Lee, George Davey Smith, Fabio Busonero, Richard J. Rose, Psychiatry, NCA - Neurobiology of mental health, EMGO - Mental health, Erasmus MC other, Epidemiology, Immunology, Clinical Child and Family Studies, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Faculty of Behavioural, Management and Social Sciences, and Academic Medical Center
Subjects: Netherlands Twin Register (NTR), medicine.medical_specialty, media_common.quotation_subject, METIS-311183, Genome-wide association study, IR-96768, mental disorders, medicine, Personality, 1000 Genomes Project, Big Five personality traits, Psychiatry, Psychiatric genetics, media_common, Depressive Disorder, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], ta1184, medicine.disease, Neuroticism, ta3124, 3. Good health, Psychiatry and Mental health, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Major depressive disorder, Psychology, Imputation (genetics), Clinical psychology
Abstract: Contains fulltext : 153372.pdf (Publisher’s version ) (Closed access) IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 x 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 x 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 x 10-12 < P < .05) and MDD (4.02 x 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.
Published: 2015

36. Heritability of Transforming Growth Factor-β1 and Tumor Necrosis Factor-Receptor Type 1 Expression and Vitamin D Levels in Healthy Adolescent Twins

Author: James Scott, John J. McGrath, Eva Birosova, Narelle K. Hansell, Nicholas G. Martin, Anjali K. Henders, Anna A. E. Vinkhuyzen, Natalie T. Mills, Grant W. Montgomery, Edna M. Byrne, Margaret J. Wright, Naomi R. Wray, Bernhard T. Baune, and Darryl W. Eyles
Subjects: Male, Psychosis, Adolescent, medicine.medical_treatment, Physiology, Cohort Studies, Transforming Growth Factor beta1, Quantitative Trait, Heritable, Sex Factors, Immune system, Reference Values, Twins, Dizygotic, medicine, Vitamin D and neurology, Humans, Genetic Predisposition to Disease, Vitamin D, Genetics (clinical), Depressive Disorder, Major, Obstetrics and Gynecology, Twins, Monozygotic, Heritability, medicine.disease, Cytokine, Receptors, Tumor Necrosis Factor, Type I, Schizophrenia, Pediatrics, Perinatology and Child Health, Cohort, Immunology, Cytokines, Major depressive disorder, Female, Gene-Environment Interaction, Queensland, Inflammation Mediators, Psychology, Biomarkers
Abstract: Cytokines and vitamin D both have a role in modulating the immune system, and are also potentially useful biomarkers in mental illnesses such as major depressive disorder (MDD) and schizophrenia. Studying the variability of cytokines and vitamin D in a healthy population sample may add to understanding the association between these biomarkers and mental illness. To assess genetic and environmental contributions to variation in circulating levels of cytokines and vitamin D (25-hydroxy vitamin D: 25(OH)D3), we analyzed data from a healthy adolescent twin cohort (mean age 16.2 years; standard deviation 0.25). Plasma cytokine measures were available for 400 individuals (85 MZ, 115 DZ pairs), dried blood spot sample vitamin D measures were available for 378 individuals (70 MZ, 118 DZ pairs). Heritability estimates were moderate but significant for the cytokines transforming growth factor-β1 (TGF-β1), 0.57 (95% CI 0.26–0.80) and tumor necrosis factor-receptor type 1 (TNFR1), 0.50 (95% CI 0.11–0.63) respectively. Measures of 25(OH)D3 were within normal range and heritability was estimated to be high (0.86, 95% CI 0.61–0.94). Assays of other cytokines did not generate meaningful results. These potential biomarkers may be useful in mental illness, with further research warranted in larger sample sizes. They may be particularly important in adolescents with mental illness where diagnostic uncertainty poses a significant clinical challenge.
Published: 2014

37. GWAS meta-analysis (N=279,930) identifies new genes and functional links to intelligence

Author: Lene Christiansen, Robert M. Bilder, Katherine E. Burdick, Tinca J. C. Polderman, Ana B. Muñoz-Manchado, Gary Donohoe, Matthew C. Keller, Stephan Ripke, Anil K. Malhotra, Delilah Zabaneh, Andrea Christoforou, Matthew A. Scult, Nikolaos Smyrnis, Scott I. Vrieze, Fred W. Sabb, Stella G. Giakoumaki, Nathan G. Skene, Ole A. Andreassen, Nicholas G. Martin, Jari Lahti, Anna C. Need, Philip R. Jansen, Todd Lencz, Emma Knowles, Peter B. Barr, Pamela DeRosse, Russell A. Poldrack, Henning Tiemeier, Sten Linnarsson, Hannah Young, Emily Drabant Conley, Dan E. Arking, Jin Yu, Grant W. Montgomery, Danielle Posthuma, Dwight Dickinson, Elizabeth T. Cirulli, Gerome Breen, Gunter Schumann, Michael Gill, Erin Burke Quinlan, Robert Plomin, Kyoko Watanabe, Joey W. Trampush, John M. Starr, Katri Räikkönen, Narelle K. Hansell, Eliza Congdon, Olav B. Smeland, Jens Hjerling-Leffler, Richard E. Straub, Aiden Corvin, Chandra A. Reynolds, Astri J. Lundervold, Bradley T. Webb, Gonçalo R. Abecasis, Jonathan R. I. Coleman, Srdjan Djurovic, Margaret J. Wright, Kjetil Sundet, Ivar Reinvang, Robert Karlsson, Deborah C. Koltai, Ina Giegling, Alex Hatzimanolis, David C. Liewald, William Ollier, Sophie van der Sluis, Edythe D. London, Tyrone D. Cannon, Thomas Espeseth, M. Arfan Ikram, Ian J. Deary, Christiaan de Leeuw, Daniel R. Weinberger, Neil Pendleton, Ornit Chiba-Falek, Jakob Kaminski, Danielle M. Dick, Panos Bitsios, Nikos C. Stefanis, Tonya White, Bettina Konte, Ida K. Karlsson, Mats Nagel, Derek W. Morris, Anke R. Hammerschlag, Swapnil Awasthi, Antony Payton, Julien Bryois, Nelson A. Freimer, Nancy L. Pedersen, Panos Roussos, Andreas Heinz, Johan G. Eriksson, Marianne Nygaard, Birgit Debrabant, Aarno Palotie, Elisabeth Widen, Aristotle N. Voineskos, Patrick Sullivan, Ingrid Melle, Dan Rujescu, Vidar M. Steen, Eva Krapohl, Katrina L. Grasby, Max Lam, Stephanie Le Hellard, Kenneth S. Kendler, Jeanne E. Savage, Sarah E. Medland, Sven Stringer, David C. Glahn, Gail Davies, Ahmad R. Hariri, Sara Hägg, and Dimitrios Avramopoulos
Subjects: Genetics, Nonsynonymous substitution, 0303 health sciences, Genome-wide association study, Biology, 03 medical and health sciences, 0302 clinical medicine, Pleiotropy, Mendelian randomization, Expression quantitative trait loci, Neuron differentiation, Gene, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association
Abstract: Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to intelligence3–7, but much about its genetic underpinnings remains to be discovered. Here, we present the largest genetic association study of intelligence to date (N=279,930), identifying 206 genomic loci (191 novel) and implicating 1,041 genes (963 novel) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and identify 89 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain and specifically in striatal medium spiny neurons and cortical and hippocampal pyramidal neurons. Gene-set analyses implicate pathways related to neurogenesis, neuron differentiation and synaptic structure. We confirm previous strong genetic correlations with several neuropsychiatric disorders, and Mendelian Randomization results suggest protective effects of intelligence for Alzheimer’s dementia and ADHD, and bidirectional causation with strong pleiotropy for schizophrenia. These results are a major step forward in understanding the neurobiology of intelligence as well as genetically associated neuropsychiatric traits.
Published: 2017
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38. Genetic Architecture of Subcortical Brain Structures in Over 40,000 Individuals Worldwide

Author: Arvin Saremi, Tomas Axelsson, Kristel R. van Eijk, Tonya White, Elena Shumskaya, Christine Macare, Christopher Chen, Neeltje E.M. van Haren, K Hegenscheid, Ingrid Melle, Benjamin S. Aribisala, Clyde Francks, Lisa R. Yanek, Konstantinos Arfanakis, Lars Nyberg, Nina Romanczuk-Seiferth, Clifford R. Jack, Thomas H. Wassink, Norman Delanty, Oscar L. Lopez, Jennifer S. Richards, Philippe Amouyel, William T. Longstreth, Michael W. Weiner, Maria J. Knol, Ralph Burkhardt, Ching-Yu Cheng, Wolfgang Hoffmann, Norbert Hosten, Alexander Teumer, Simone Reppermund, Markus M. Nöthen, Tien Yin Wong, Maria del C. Valdés Hernández, Bernd Kraemer, Murali Sargurupremraj, Amelia A. Assareh, Jessika E. Sussmann, Gabriel Cuellar-Partida, Ian J. Deary, Ganesh Chauhan, Christopher R.K. Ching, Arno Villringer, Dalia Kasperaviciute, Han G. Brunner, Srdjan Djurovic, Lachlan T. Strike, Albert V. Smith, Lars T. Westlye, Paul A. Nyquist, Bertram Müller-Myhsok, Phil Lee, Qiong Yang, Herve Lemaitre, Andreas Meyer-Lindenberg, Vidar M. Steen, Marc M. Bohlken, Rachel M. Brouwer, Charles DeCarli, Mar Matarin, Fabrice Crivello, Henry Völzke, Manuel Mattheisen, Bruno Vellas, Loes M. Olde Loohuis, Sudha Seshadri, Claudia L. Satizabal, Sebastian Mohnke, David C. Liewald, Li Shen, Kwangsik Nho, Simon E. Fisher, Deborah Janowitz, Wiro J. Niessen, Matthew J. Huentelman, Sylvane Desrivières, Ole A. Andreassen, Evan Fletcher, Christiane Wolf, Vilmundur Gudnason, Alejandro Arias-Vasquez, Charles C. White, Joshua C. Bis, Pauline Maillard, Ingrid Agartz, Oliver Grimm, Matthias Nauck, Andrew M. McIntosh, Iryna O. Fedko, Gianpiero L. Cavalleri, Andreas Heinz, Tulio Guadalupe, Andrew D. Johnson, Daan van Rooij, Thomas W. Mühleisen, Jessica A. Turner, Marieke Klein, Jia Yu Koh, Avram J. Holmes, Saud Alhusaini, Douglas N. Greve, Roberto Roiz-Santiañez, Nic J.A. van der Wee, Irina Filippi, Hans van Bokhoven, Miguel E. Rentería, Andrew J. Saykin, Marjolein M.J. van Donkelaar, Dan J. Stein, Randy L. Gollub, Sanjay M. Sisodiya, Honghuang Lin, Aaron Goldman, Patrizia Mecocci, Thomas Espeseth, Barbara Franke, Unn K. Haukvik, Theo G.M. van Erp, Venkata S. Mattay, Jonathan C Ipser, Catharina A. Hartman, Florian Holsboer, Saskia P. Hagenaars, Benedicto Crespo-Facorro, Manon Bernard, Jerome I. Rotter, Louis N. Vinke, Nastassja Koen, Vince D. Calhoun, Anders M. Dale, Dennis van der Meer, Jordan W. Smoller, Debra A. Fleischman, Janita Bralten, Hannah J. Jones, Lavinia Athanasiu, Hilleke E. Hulshoff Pol, Brenda W.J.H. Penninx, Peter R. Schofield, Roel A. Ophoff, J Wardlaw, Sven J. van der Lee, Katie L. McMahon, Esther Walton, Nicholas G. Martin, Gunter Schumann, Katharina Wittfeld, Perminder S. Sachdev, André G. Uitterlinden, Christophe Tzourio, Pieter J. Hoekstra, Roberto Toro, Henry Brodaty, Marcella Rietschel, David Ames, George Davey Smith, G. Bruce Pike, Alexa S. Beiser, Zdenka Pausova, Simon Lovestone, Robert C. Green, Greig I. de Zubicaray, Stephen M. Lawrie, Mark E. Bastin, Marco P. Boks, M. Mallar Chakravarty, Magda Tsolaki, Myriam Fornage, Nanda Rommelse, Andre F. Marquand, Anbupalam Thalamuthu, Helena Schmidt, Jason L. Stein, Bruce M. Psaty, Jan K. Buitelaar, Jean-Luc Martinot, Kazima B. Bulayeva, Henrik Walter, Xueqiu Jian, Yasaman Saba, Saima Hilal, Paul M. Thompson, Tamara B. Harris, Jaap Oosterlaan, Marie-José van Tol, Joshua L. Roffman, Bernard Mazoyer, Shuo Li, Nhat Trung Doan, Qiang Chen, John B.J. Kwok, Najaf Amin, Diana Tordesillas-Gutiérrez, Eco J. C. de Geus, Meike W. Vernooij, Andrew J. Schork, Susanne Erk, Daniel R. Weinberger, Grant W. Montgomery, Jean Shin, James T. Becker, Martine Hoogman, Philip L. De Jager, Dirk J. Heslenfeld, Derrek P. Hibar, Narelle K. Hansell, Andrew Simmons, Micael Andersson, Lucija Abramovic, Dorret I. Boomsma, Allison Stevens, Wei Wen, A. Veronica Witte, Owen Carmichael, Jayandra J. Himali, Asta Håberg, Hieab H.H. Adams, Nynke A. Groenewold, Sven Cichon, Wiepke Cahn, Lianne Schmaal, Shannon L. Risacher, Erik G. Jönsson, Shahrzad Kharabian Masouleh, Oliver Gruber, Tianye Jia, Hilkka Soininen, M. Kamran Ikram, Markus Loeffler, Philipp G. Sämann, Sungeun Kim, Jingyun Yang, Iwona Kłoszewska, Ryota Kanai, Christopher D. Whelan, Massimo Pandolfo, Dick J. Veltman, Diane M. Becker, Anouk den Braber, Hans J. Grabe, Neda Jahanshad, Yanhui Hu, Anita L. DeStefano, Beng-Choon Ho, Stephanie Le Hellard, Cornelia M. van Duijn, Georg Homuth, Tomáš Paus, Stéphanie Debette, Nicola J. Armstrong, Jouke-Jan Hottenga, Eric Westman, Tom V. Lee, Sarah E. Medland, Randy L. Buckner, Benno Pütz, Edith Hofer, Steven G. Potkin, Albert Hofman, Dennis van 't Ent, Sudheer Giddaluru, Tatiana Foroud, Guillén Fernández, John D. Eicher, Gareth E. Davies, Thomas H. Mosley, Michelle Luciano, Lenore J. Launer, Joshua W. Cheung, Markus Scholz, D. Höhn, Thomas Wolfers, Reinhold Schmidt, Arthur W. Toga, René S. Kahn, Nazanin Karbalai, Yuri Milaneschi, Margaret J. Wright, Martina Papmeyer, David A. Bennett, M. Arfan Ikram, Stefan Ehrlich, Marcel P. Zwiers, Karen A. Mather, and Joshua M. Shulman
Subjects: Candidate gene, Globus pallidus, nervous system, Putamen, Thalamus, Caudate nucleus, Synaptic signaling, Nucleus accumbens, Biology, Bioinformatics, Neuroscience, Genetic architecture
Abstract: Subcortical brain structures are integral to motion, consciousness, emotions, and learning. We identified common genetic variation related to the volumes of nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen, and thalamus, using genome-wide association analyses in over 40,000 individuals from CHARGE, ENIGMA and the UK-Biobank. We show that variability in subcortical volumes is heritable, and identify 25 significantly associated loci (20 novel). Annotation of these loci utilizing gene expression, methylation, and neuropathological data identified 62 candidate genes implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Published: 2017

39. Ninety-nine independent genetic loci influencing general cognitive function include genes associated with brain health and structure (N = 280,360)

Author: Nancy L. Pedersen, John M. Starr, Kjetil Sundet, Qiong Yang, Nicole A. Kochan, Beverly Gwen Windham, Ida K. Karlsson, Daniel E. Gustavson, Jerome I. Rotter, Antony Payton, M. Arfan Ikram, Alison D. Murray, Edith Hofer, Ozren Polasek, Markus Leber, Will Longstreth, Stephanie Le Hellard, Peter W. Schofield, Raha Pazoki, Janie Corley, Max Lam, Deborah K. Attix, Hieab H.H. Adams, Tobias Luck, Ian J. Deary, Panos Roussos, Amelia A. Assareh, Katja Petrovic, Dwight Dickinson, Elizabeth T. Cirulli, Thomas Espeseth, Richard J. Rose, Annette L. Fitzpatrick, Robert M. Bilder, Rodney J. Scott, Katherine E. Burdick, William S. Kremen, Christophe Tzourio, Richard E. Straub, Thomas H. Mosley, Michael Griswold, Ulman Lindenberger, Peter R. Schofield, Riccardo E. Marioni, Stéphanie Debette, Jennifer A. Smith, M. Kamran Ikram, Pamela DeRosse, Russell A. Poldrack, Teemu Palviainen, Panos Bitsios, Nikos C. Stefanis, Anu Loukola, Nikolaos Smyrnis, Todd Lencz, Michelle Luciano, Robert Karlsson, Bettina Konte, Dan Rujescu, Mika Kähönen, James F. Wilson, Steven T. Turner, David A. Bennett, Jingyun Yang, Cornelia M. van Duijn, David S. Knopman, Harry Campbell, R. F. Gottesman, Vidar M. Steen, Nicola J. Armstrong, Alfredo Ramirez, Ina Giegling, Jari Lahti, Marisa Koini, Tyrone D. Cannon, Gerardo Heiss, Ian Ford, Vilmundur Gudnason, Alex Hatzimanolis, Joshua C. Bis, Albert V. Smith, David Ames, Jan Bressler, Catriona L. K. Barnes, Emily Drabant Conley, Raymond Noordam, Ornit Chiba-Falek, Michael Gill, Simone Reppermund, Katri Räikkönen, Christopher Oldmeadow, Kent D. Taylor, Holger Wagner, Claudia L. Satizabal, Chandra A. Reynolds, Tian Liu, Daniel R. Weinberger, Neil Pendleton, Scott D. Gordon, Eric Boerwinkle, Saskia P. Hagenaars, Andrew M. McIntosh, Igor Rudan, Joey W. Trampush, John Attia, Michael Wagner, K. Hoyan Wen, Judith A. Okely, Aristotle N. Voineskos, Patricia A. Boyle, Danielle M. Dick, Anna C. Need, Markus Scholz, Luca Kleineidam, Aiden Corvin, Ingrid Melle, Margaret J. Wright, Helena Schmidt, Leo-Pekka Lyytikäinen, Natalie Terzikhan, Stuart J. Ritchie, He Gao, Anne C. Böhmer, Dan E. Arking, Narelle K. Hansell, Nicholas G. Martin, Fred W. Sabb, Nathan A. Gillespie, Evangelos Evangelou, Bruce M. Psaty, Anders Lundquist, Oscar L. Lopez, Emma Knowles, Matthew C. Keller, Henry Brodaty, Julian N. Trollor, Gary Donohoe, Ivar Reinvang, Ari Ahola-Olli, Tamara B. Harris, André G. Uitterlinden, David R. Weir, Abbas Dehghan, Sarah E. Harris, P. Eline Slagboom, Chloe Fawns-Ritchie, Paul Elliott, William Ollier, Edythe D. London, Anders M. Dale, Jaakko Kaprio, Catharine R. Gale, Karen A. Mather, Aarno Palotie, Stella G. Giakoumaki, Sven J. van der Lee, Jeannette Simino, Elisabeth Widen, Teresa Lee, Sudheer Giddaluru, Anil K. Malhotra, Philippe Amouyel, Caroline Hayward, Shuo Li, Goran Papenberg, Steffi G. Riedel-Heller, Wei Zhao, Nelson A. Freimer, Simon R. Cox, Yasaman Saba, Andrea Christoforou, Johan G. Eriksson, Eliza Congdon, David J. Porteous, Matthew A. Scult, Eero Vuoksimaa, Veronique Vitart, Derek W. Morris, Sharon L.R. Kardia, Elizabeth G. Holliday, Peter K. Joshi, Suvi P. Rovio, Astri J. Lundervold, J. Wouter Jukema, Aicha Soumare, Stella Trompet, Annette M. Hartmann, Ole A. Andreassen, Erin B. Ware, Matthias Schmid, Perminder S. Sachdev, Grant W. Montgomery, Lars Bertram, Philip L. De Jager, Olli T. Raitakari, Terho Lehtimäki, Arno Villringer, Srdjan Djurovic, David C. Liewald, Sudha Seshadri, Gail Davies, Ahmad R. Hariri, Sara Hägg, Lars Nyberg, Dimitrios Avramopoulos, Muralidharan Sargurupremraj, W. David Hill, Shu-Chen Li, Leonie Weinhold, David J. Stott, David C. Glahn, John B.J. Kwok, Ioanna Tzoulaki, Reinhold Schmidt, Najaf Amin, Lenore J. Launer, Jin Yu, Jessica D. Faul, Adele M. Taylor, Anbupalam Thalamuthu, and Alison Pattie
Subjects: Genetics, 0303 health sciences, media_common.quotation_subject, Longevity, Genetic data, Cognition, Heritability, Significant snps, Biology, Biobank, 03 medical and health sciences, 0302 clinical medicine, Trait, Gene, 030217 neurology & neurosurgery, 030304 developmental biology, media_common
Abstract: General cognitive function is a prominent human trait associated with many important life outcomes1,2, including longevity3. The substantial heritability of general cognitive function is known to be polygenic, but it has had little explication in terms of the contributing genetic variants4,5,6. Here, we combined cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N=280,360; age range = 16 to 102). We found 9,714 genome-wide significant SNPs (P−8) in 99 independent loci. Most showed clear evidence of functional importance. Among many novel genes associated with general cognitive function wereSGCZ,ATXN1,MAPT,AUTS2, andP2RY6. Within the novel genetic loci were variants associated with neurodegenerative disorders, neurodevelopmental disorders, physical and psychiatric illnesses, brain structure, and BMI. Gene-based analyses found 536 genes significantly associated with general cognitive function; many were highly expressed in the brain, and associated with neurogenesis and dendrite gene sets. Genetic association results predicted up to 4% of general cognitive function variance in independent samples. There was significant genetic overlap between general cognitive function and information processing speed, as well as many health variables including longevity.
Published: 2017

40. Investigating the relationship between iron and depression

Author: Gerard J. Byrne, Enda M. Byrne, Natalie T. Mills, Lucía Colodro-Conde, James Scott, Naomi R. Wray, Margaret J. Wright, Anjali K. Henders, Beben Benyamin, Narelle K. Hansell, Anna A. E. Vinkhuyzen, Grant W. Montgomery, Nicholas G. Martin, Baptiste Couvy-Duchesne, Robert Maier, John Whitfield, Mills, Natalie T, Maier, Robert, Whitfield, John B, Wright, Margaret J, Colodro-Conde, Lucia, Byrne, Enda M, Scott, James G, Byrne, Gerard J, Hansell, Narelle K, Vinkhuyzen, Anna AE, CouvyDuchesne, Baptiste, Montgomery, Grant W, Henders, Anjali K, Martin, Nicholas G, Wray, Naomi R, and Benyamin, Beben
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Adolescent, Iron, Poison control, Linkage Disequilibrium, 03 medical and health sciences, Young Adult, 0302 clinical medicine, iron, transferrin saturation, medicine, Humans, transferrin, Genetic Predisposition to Disease, Registries, Psychiatry, Biological Psychiatry, Genetic association, chemistry.chemical_classification, Depressive Disorder, Major, biology, medicine.diagnostic_test, Transferrin saturation, ferritin, Australia, Transferrin, medicine.disease, Ferritin, Psychiatry and Mental health, 030104 developmental biology, chemistry, Cohort, depression, Ferritins, biology.protein, Serum iron, Major depressive disorder, Female, Queensland, Psychology, 030217 neurology & neurosurgery, Demography, Genome-Wide Association Study
Abstract: Lower levels of circulating iron have been associated with depression. Our objective was to investigate the phenotypic and genetic relationship between measures of circulating levels of iron (serum iron, transferrin, transferrin saturation, and ferritin) and depressive symptoms. Data were available from ongoing studies at QIMR Berghofer Medical Research Institute (QIMRB), including twin adolescents (mean age 15.1 years, standard deviation (SD) 3.2 years), and twin adults (mean age 23.2 years, SD 2.2 years). In the adolescent cohort, there were 3416 participants from 1688 families. In the adult cohort there were 9035 participants from 4533 families. We estimated heritabilities of, and phenotypic and genetic correlations between, traits. We conducted analyses that linked results from published large-scale genome-wide association studies (including iron and Major Depressive Disorder) with our study samples using single SNP and multi-SNP genetic risk score analyses, and LD score regression analyses. In both cohorts, measures of iron, transferrin, transferrin saturation, and log 10 of ferritin (L10Fer) were all highly heritable, while depressive measures were moderately heritable. In adolescents, depression measures were higher in those in the middle 10th versus top 10th percentile of transferrin saturation measures (p = 0.002). Genetic profile risk scores of the iron measures were not significantly associated with depression in study participants. LD score analyses showed no significant genetic relationship between iron and depression. Genetic factors strongly influence iron measures in adolescents and adults. Using several different strategies we find no evidence for a genetic contribution to the relationship between blood measures of iron and measures of depression. Refereed/Peer-reviewed
Published: 2017

41. Novel genetic loci associated with hippocampal volume

Author: Benjamin S. Aribisala, Marjolein M.J. van Donkelaar, Randy L. Gollub, Rachel M. Brouwer, Norman Delanty, Tomas Axelsson, Oscar L. Lopez, Thomas Espeseth, Alejandro Arias-Vasquez, Kristel R. van Eijk, Tien Yin Wong, Jeroen van der Grond, Georg Homuth, James T. Becker, Sebastian Guelfi, Anton J. M. de Craen, Bruno Vellas, Christopher R.K. Ching, Charles C. DeCarli, Janita Bralten, Lars T. Westlye, Ryota Hashimoto, Sampath Arepalli, Bertram Müller-Myhsok, Loes M. Olde Loohuis, Sudha Seshadri, Simon E. Fisher, K Hegenscheid, Konstantinos Arfanakis, Zdenka Pausova, Robert C. Green, Simone Reppermund, Katie L. McMahon, Ashley Beecham, Daan van Rooij, Marcel P. Zwiers, Karen A. Mather, Randy L. Buckner, Edith Hofer, Marcella Rietschel, Fabrice Crivello, Ronald H. Zielke, G. Bruce Pike, Thomas W. Mühleisen, Myriam Fornage, Kazutaka Ohi, Gareth E. Davies, Chantal Depondt, Gabriel Cuellar-Partida, Iryna O. Fedko, Peter R. Schofield, Steven G. Potkin, Albert Hofman, Paul M. Thompson, Wiro J. Niessen, Deborah Janowitz, Nicholas G. Martin, Li Shen, Mina Ryten, Meike W. Vernooij, Michael E. Weale, Tonya White, Dennis van 't Ent, Sudheer Giddaluru, Nanda Rommelse, Wei Wen, Sven J. van der Lee, Eco J. C. de Geus, Aaron Goldman, Joanne E. Curran, Qiang Chen, Jean Shin, Wayne C. Drevets, Thomas H. Mosley, Matthias Nauck, Massimo Pandolfo, Anders M. Dale, Paul A. Nyquist, Girma Woldehawariat, Francis J. McMahon, Najaf Amin, Emma J. Rose, Norbert Hosten, David J. Stott, Sigurdur Sigursson, Andrew J. Saykin, M. Kamran Ikram, Pieter J. Hoekstra, Neda Jahanshad, Grant W. Montgomery, Michael Weiner, Aad van der Lugt, Esther Walton, Gunter Schumann, Clyde Francks, Narelle K. Hansell, Xinmin Liu, Herve Lemaitre, Cornelia M. van Duijn, Ralph L. Sacco, Clinton B. Wright, Arvin Saremi, Clifford R. Jack, Andre G. Uitterlinden, G. Donohoe, Tomáš Paus, Michael Griswold, Peter T. Fox, Alan B. Zonderman, Lukas Pirpamer, Christiane Wolf, Aiden Corvin, Shannon L. Risacher, Ian Ford, Philippe Amouyel, Henrik Walter, Beng-Choon Ho, William T. Longstreth, M. Arfan Ikram, Hieab H.H. Adams, Colin Smith, Sungeun Kim, Simon Lovestone, Stefan Ehrlich, Benno Pütz, Markus M. Nöthen, Susana Muñoz Maniega, Ian J. Deary, Elena Shumskaya, Susan H. Blanton, Jerome I. Rotter, Neeltje E.M. van Haren, Mar Matarin, I. Kloszewska, Ganesh Chauhan, Anita L. DeStefano, Barbara Franke, Lars Nyberg, Tatiana Foroud, Tianye Jia, Manon Bernard, Unn K. Haukvik, Rebecca F. Gottesman, Srdjan Djurovic, Ching-Yu Cheng, Lachlan T. Strike, Alex P. Zijdenbos, Jouke-Jan Hottenga, Vince D. Calhoun, Yuri Milaneschi, David C. Glahn, Phil Lee, Amelia A. Assareh, Adaikalavan Ramasamy, Emma Sprooten, Debra A. Fleischman, David R. McKay, J. Raphael Gibbs, Bruce M. Psaty, Kazima B. Bulayeva, Bryan J. Traynor, Vilmundur Gudnason, Jessika E. Sussmann, Alexander Teumer, Guillén Fernández, Katharina Wittfeld, Christophe Tzourio, Dennis van der Meer, Wolfgang Hoffmann, Sebastian Mohnke, David C. Liewald, Jordan W. Smoller, Theo G.M. van Erp, Marcel Van Der Brug, Dara M. Cannon, Lenore J. Launer, D. Ames, Juan C. Troncoso, Brenda W.J.H. Penninx, Dhananjay Vaidya, Thomas D. Dyer, Marie-José van Tol, Han G. Brunner, Andrew Singleton, Lavinia Athanasiu, Adam M. Brickman, Eric Westman, P. Mecocci, Sandra Barral, Dick J. Veltman, Catharina A. Hartman, Benedicto Crespo-Facorro, Alexa S. Beiser, Vincent Chouraki, Nhat Trung Doan, Marieke Klein, Jaap Oosterlaan, Natalie A. Royle, John B.J. Kwok, Saud Alhusaini, Ingrid Melle, Roberto Toro, Ravi Duggirala, Allissa Dillman, Reinhold Schmidt, Lisa R. Yanek, Anbupalam Thalamuthu, Helena Schmidt, Derrek P. Hibar, Albert V. Smith, Jean-Luc Martinot, Thomas H. Wassink, Jennifer S. Richards, Oliver Martinez, Joshua L. Roffman, Sylvane Desrivières, Hilkka Soininen, Rene L. Olvera, Ole A. Andreassen, Diana Tordesillas-Gutiérrez, Claudia L. Satizabal, Owen Carmichael, Lianne Schmaal, Bernd Kraemer, Martine Hoogman, Daniah Trabzuni, Oliver Grimm, Andrew M. McIntosh, René S. Kahn, Nazanin Karbalai, Margaret J. Wright, Harald H.H. Göring, Martina Papmeyer, Roberto Roiz-Santiañez, Luigi Ferrucci, David A. Bennett, Kwangsik Nho, Gianpiero L. Cavalleri, Andreas Meyer-Lindenberg, Masashi Ikeda, Avram J. Holmes, Greig I. de Zubicaray, Andreas Heinz, Tatjana Rundek, Maria del C. Valdés Hernández, Dalia Kasperaviciute, Dan L. Longo, Matthew J. Huentelman, Wiepke Cahn, Beverly G. Windham, Michael A. Nalls, Philipp G. Sämann, Stella Trompet, Vidar M. Steen, Marc M. Bohlken, Christopher D. Whelan, Hilleke E. Hulshoff Pol, Susanne Erk, Dorret I. Boomsma, Dirk J. Heslenfeld, Masaki Fukunaga, D. Hoehn, Stephen M. Lawrie, Mark E. Bastin, Marco P. Boks, M. Mallar Chakravarty, M. R. Cookson, C. McDonald, Magda Tsolaki, Badri N. Vardarajan, Jason L. Stein, Jan K. Buitelaar, Erik G. Jönsson, Oliver Gruber, Robert Johnson, Jingyun Yang, Joshua C. Bis, J. Wouter Jukema, Tulio Guadalupe, Nina Romanczuk-Seiferth, Kjetil Nordbø Jørgensen, Henry Brodaty, Diane M. Becker, Anouk den Braber, Allison C. Nugent, Thomas Wolfers, John Hardy, Joanna M. Wardlaw, Michelle Luciano, Christine Macare, Dena G. Hernandez, D. Morris, John Blangero, Andrew J. Schork, Daniel R. Weinberger, Johanna Hass, Andrew Simmons, Micael Andersson, Lucija Abramovic, David S. Knopman, Mark Jenkinson, Roel A. Ophoff, Sanjay M. Sisodiya, Boris A. Gutman, Asta Håberg, Stephanie Le Hellard, Stéphanie Debette, Nicola J. Armstrong, Sarah E. Medland, Hans J. Grabe, Henry Völzke, Thomas E. Nichols, Manuel Mattheisen, Sven Cichon, Venkata S. Mattay, Ingrid Agartz, Stefan Ropele, Lorna M. Lopez, Hans van Bokhoven, Philip L. De Jager, Miguel E. Rentería, Laura Almasy, Arthur W. Toga, Michael Czisch, Florian Holsboer, Ryota Kanai, Nic J.A. van der Wee, Peter Kochunov, Perminder S. Sachdev, Andre F. Marquand, Christian Enzinger, Anderson M. Winkler, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Metacohorts Consortium, Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, sans affiliation, QIMR Berghofer Medical Research Institute, University of Washington [Seattle], Department of Psychiatry, Donders Centre for Neuroscience, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University Medical Center [Utrecht], Department of Neurology and Neurosurgery [Montreal], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Sahlgrenska University Hospital [Gothenburg], Department of Biomedical Engineering, Illinois Institute of Technology (IIT), Rush University Medical Center [Chicago], University of Edinburgh, Lagos State University (LASU), Assistance Publique - Hôpitaux de Marseille (APHM), University of Oslo (UiO), Department of medical sciences, Uppsala University-Molecular Medicine-Science for Life Laboratory, John P. Hussman Institute for Human Genomics, University of Miami Leonard M. Miller School of Medicine (UMMSM), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), Douglas Mental Health University Institute, McGill University = Université McGill [Montréal, Canada], Université Lille Nord de France (COMUE), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe d'imagerie neurofonctionnelle (GIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Haukeland University Hospital, University of Bergen (UiB), Ames Laboratory [Ames, USA], Iowa State University (ISU)-U.S. Department of Energy [Washington] (DOE), Johns Hopkins University School of Medicine [Baltimore], Language and Genetics Department [Nijmegen], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, International Max Planck Research School for Language Sciences (IMPRS ), Laboratory of Neuro Imaging [Los Angeles] (LONI), Department of Mathematics [UCLA], Georgia Institute of Technology [Atlanta], Medizinische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Germany, Greifswald University Hospital, Beijing Normal University (BNU), Aalborg University [Denmark] (AAU), UCL Institute of Neurology and Epilepsy Society, Department of Medicine, Imperial College London, Service d'Endocrinologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Medstar Research Institute, Clinical And Experimental Epilepsy, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Genomics, Life and Brain Center, University of Bonn, Institute of Human Genetics, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], VU University Medical Center [Amsterdam], Indiana University School of Medicine, Indiana University System, Indiana Alzheimer Disease Center, Indiana University System-Indiana University System, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Department of Neurology, Statistical Genetics Group, Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], Department of Neurology [Austria], Medical University Graz, Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, INSERM, Neuroepidemiology U708, Bordeaux, France, Department of Neurosciences [San Diego], University of California [San Diego] (UC San Diego), Department of Cognitive Sciences [San Diego], Wuhan University [China], Plymouth University, Dpt of Psychiatry [New Haven], Yale University School of Medicine, Queensland Institute of Medical Research, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Department of Genetics, King Faisal Specialist Hospital and Research Centre, Depts of Radiology, Leiden University Medical Center (LUMC), University of Twente [Netherlands], Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), RCMG Ghent, Universiteit Gent = Ghent University [Belgium] (UGENT), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), National Institutes of Health [Bethesda] (NIH), Biospective [Montréal], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Université de Lille, Department of Clinical Genetics, Department of Experimental Physics, National University of Ireland Maynooth (Maynooth University), Texas Biomedical Research Institute [San Antonio, TX], The University of Texas Health Science Center at Houston (UTHealth), 849 Department of Human Genetics, Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Dementia Collaborative Research Centre, Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Department of Psychiatry [Boston], Massachusetts General Hospital [Boston], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], The Mind Research Network, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Division of Molecular and Cellular Therapeutics, Northwestern Polytechnical University [Xi'an] (NPU), Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Division of Medical Genetics, University of Basel (Unibas), Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Trinity College Dublin-St. James's Hospital, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], York Structural Biology Laboratory, Department of Chemistry, University of York [York, UK], Harvard Medical School [Boston] (HMS), Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], School of Psychology, University of Queensland, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratory of Neurogenetics, Department of Genomics, Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), École des hautes études en sciences sociales (EHESS), Department of Radiology, Mayo Clinic, Robertson Centre for Biostatistics, University of Glasgow, Human Genetics Center, Department of Medical and Molecular Genetics, Rensselaer Polytechnic Institute (RPI), Department of Physics, Okayama University, Okayama University, University of New Haven [Connecticut], Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Public Health Genomics Unit, Department of Mathematics, University of Colorado, University of Colorado [Boulder], Faculty of Medicine, University of Iceland [Reykjavik], Icelandic Heart Association, Kopavogur, Iceland., University of Science, VNU-HCM, University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Department of Medical Genetics, HMNC Brain Health, University of Oxford [Oxford], University of Florida [Gainesville] (UF), Göteborgs Universitet (GU), Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Brain Centre Rudolf Magnus [Utrecht], School of Psychology, University of Sussex, Brighton BN1 9QH, UK, University of Sussex, Institute of Cognitive Neuroscience, University College of London [London] (UCL), Medical University of Łódź (MUL), Mayo Clinic [Rochester], University of Maryland School of Medicine, University of Maryland System-University of Maryland System-University of Maryland [Baltimore County] (UMBC), University of Maryland System, School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Université de Cergy Pontoise (UCP), Université Paris-Seine, Lymphocyte Cell Biology Unit, Laboratory of Genetics, Psychiatry Institute, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Department of Health and Human Services, Department of Life Sciences, Mathematical Sciences Institute (MSI), Australian National University (ANU), Centre for Advanced Imaging, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia (UNIPG), Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Medical Faculty [Mannheim], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, University of Mississippi Medical Center (UMMC), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Institute of Clinical Chemistry and Laboratory Medicine, Department of Statistics [Coventry], University of Warwick [Coventry], Delft University of Technology (TU Delft), Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), Osaka University [Osaka], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Cedars-Sinai Medical Center, Politecnico di Milano [Milan] (POLIMI), University of Applied Sciences [Munich], Dpt of Pharmacology and Personalised Medicine [Maastricht], Maastricht University [Maastricht], Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, National Institute of Aging, 3rd Department of Neurology, Aristotle University of Thessaloniki-General Hospital of Thessaloniki George Papanikolaou, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Genentech, Inc. [San Francisco], Psychiatry and Leiden Institute for Brain and Cognition, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Community Medicine, Berlin School of Mind and Brain [Berlin], Humboldt-Universität zu Berlin, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Centre for Population Health Sciences, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet [Stockholm], University of Pretoria [South Africa], University of Missouri [Columbia] (Mizzou), University of Missouri System, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], University of Southern California (USC), University of California (UC)-University of California (UC), Sans affiliation, Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], University of Toronto, Radboud University [Nijmegen], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universität Bonn = University of Bonn, Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), Yale School of Medicine [New Haven, Connecticut] (YSM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), King Faisal Specialist Hospital and Research Centre (KFSH & RC), Universiteit Leiden-Universiteit Leiden, University of Twente, University of California [Irvine] (UC Irvine), Universiteit Gent = Ghent University (UGENT), Centre épigénétique et destin cellulaire (EDC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], University of Oxford, University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Università degli Studi di Perugia = University of Perugia (UNIPG), University Hospital Mannheim | Universitätsmedizin Mannheim, Universität Leipzig-Universität Leipzig, University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, University of Eastern Finland, Universiteit Leiden, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt University Of Berlin, Radboud University [Nijmegen]-Radboud University [Nijmegen], School of Medicine / Clinical Medicine, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Other departments, Adult Psychiatry, ARD - Amsterdam Reproduction and Development, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], McGill University-McGill University, Sahlgrenska University Hospital, McGill University, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), University of Bergen (UIB), Iowa State University (ISU)-U.S. Department of Energy (DOE), Beijing Normal University, Karakter Child and Adolescent Psychiatry University Center Nijmegen, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Gènes, Synapses et Cognition, Ghent University [Belgium] (UGENT), National University of Ireland Maynooth (NUIM), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Okayama University [Okayama], University of Florida [Gainesville], Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Aristotle University of Thessaloniki-G. Papanikolaou Hospital, Humboldt Universität zu Berlin, University of Missouri [Columbia], Epidemiology, Radiology & Nuclear Medicine, Medical Informatics, Internal Medicine, Neurology, Biological Psychology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, Cognitive Psychology, IBBA, APH - Personalized Medicine, Amsterdam Neuroscience - Brain Imaging, MUMC+: DA Klinische Genetica (5), Klinische Genetica, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Anatomy and neurosciences, APH - Digital Health, Hal, GIN, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Universidad de Cantabria, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: Male, Netherlands Twin Register (NTR), Genome-wide association study, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit, Spatial memory, 0302 clinical medicine, 610 Medicine & health, Child, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Episodic memory, Aged, 80 and over, Subiculum, 220 Statistical Imaging Neuroscience, COMMON VARIANTS, ALZHEIMERS-DISEASE, ddc:500, Alzheimer's disease, genetics [Methionine Sulfoxide Reductases], Science, Locus (genetics), genetics [Protein-Serine-Threonine Kinases], Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Alzheimer Disease, ASTN2 protein, human, Humans, GENOME-WIDE ASSOCIATION, METAANALYSIS, Aged, Glycoproteins, Dentate gyrus, MEMORY, medicine.disease, R1, 030104 developmental biology, nervous system, Genetic Loci, MSRB3 protein, human, 030217 neurology & neurosurgery, 0301 basic medicine, General Physics and Astronomy, genetics [Alzheimer Disease], Hippocampal formation, Hippocampus, Genome-wide association studies, Taugasjúkdómar, Cohort Studies, DPP4 protein, human, TEMPORAL-LOBE EPILEPSY, BRAIN-REGIONS, genetics [Dipeptidyl Peptidase 4], genetics [Nerve Tissue Proteins], Genetics, Multidisciplinary, Neurodegenerative diseases, BIPOLAR DISORDER, Organ Size, Middle Aged, SUBFIELDS, Protein-Serine-Threonine Kinases, growth & development [Hippocampus], Female, genetics [Glycoproteins], Microtubule-Associated Proteins, Medical Genetics, Neuroinformatics, Adult, genetics [Microtubule-Associated Proteins], Adolescent, SUSCEPTIBILITY LOCI, Dipeptidyl Peptidase 4, genetics [Protein Serine-Threonine Kinases], Nerve Tissue Proteins, Bioinformatik och systembiologi, Protein Serine-Threonine Kinases, Biology, physiopathology [Alzheimer Disease], 150 000 MR Techniques in Brain Function, Young Adult, MAST4 protein, human, medicine, Journal Article, Erfðafræði, Genetic Predisposition to Disease, ddc:610, Medicinsk genetik, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Bioinformatics and Systems Biology, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Rannsóknir, General Chemistry, Methionine Sulfoxide Reductases, 150 Psychology, Genome-Wide Association Study
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness., published version, peerReviewed
Published: 2017

42. Novel genetic loci underlying human intracranial volume identified through genome-wide association

Author: G. Bruce Pike, Marcel P. Zwiers, Andreas Meyer-Lindenberg, Jeroen van der Grond, Randy L. Gollub, Karen A. Mather, Andrew J. Schork, Vidar M. Steen, Marc M. Bohlken, Nhat Trung Doan, Derek W. Morris, John B.J. Kwok, Emma J. Rose, Johanna Hass, Andrew Simmons, Tian Ge, Reinhold Schmidt, Micael Andersson, Ian J. Deary, Christopher Chen, Derrek P. Hibar, Simon E. Fisher, Lucija Abramovic, Marcella Rietschel, Edith Hofer, Simon Lovestone, Clyde Francks, Christopher R.K. Ching, Srdjan Djurovic, Lachlan T. Strike, Lorna M. Lopez, Rene L. Olvera, Owen Carmichael, M. Arfan Ikram, Andre F. Marquand, Christine Macare, W.T. Longstreth, Philippe Amouyel, Aaron L. Goldman, Wolfgang Hoffmann, Philip L. De Jager, David C. Liewald, Harald H H Göring, Aad van der Lugt, David Ames, Neeltje E.M. van Haren, Lars Nyberg, Nina Romanczuk-Seiferth, Lukas Pirpamer, Stefan Ehrlich, Alexa S. Beiser, Lianne Schmaal, Hilkka Soininen, Mark Jenkinson, Kazima B. Bulayeva, Anderson M. Winkler, Mike A. Nalls, Diana Tordesillas-Gutiérrez, Martine Hoogman, Lars T. Westlye, Loes M. Olde Loohuis, Andrew Singleton, Gabriel Cuellar-Partida, Randy L. Buckner, Dorret I. Boomsma, Dena G. Hernandez, Steven G. Potkin, Sudha Seshadri, Bertram Müller-Myhsok, D. Hoehn, Gareth E. Davies, Chantal Depondt, Henrik Walter, Michael E. Weale, Deborah Janowitz, Susanne Erk, Iryna O. Fedko, Daniel R. Weinberger, Nic J A van der Wee, Jean-Luc Martinot, Jessica A. Turner, Marieke Klein, Sandra Barral, Sebastian Mohnke, Albert Hofman, Ingrid Melle, Saud Alhusaini, Vincent Chouraki, Stephen M. Lawrie, Mark E. Bastin, Juan C. Troncoso, Jean Shin, Wiro J. Niessen, Diane M. Becker, Laura Almasy, Anders M. Dale, Benjamin S. Aribisala, Dennis van 't Ent, Marco P. Boks, M. Mallar Chakravarty, Paul M. Thompson, David Reese McKay, Michael Griswold, John Blangero, Narelle K. Hansell, Eco J. C. de Geus, Paul A. Nyquist, Susana Muñoz Maniega, Sampath Arepalli, Tatjana Rundek, Dan L. Longo, Anton J. M. de Craen, Rebekah McWhirter, Nazanin Mirza-Schreiber, Henning Tiemeier, Girma Woldehawariat, Sven Cichon, Irene Pappa, Amelia A. Assareh, Sudheer Giddaluru, Pieter J. Hoekstra, Hieab H.H. Adams, Hilleke E. Hulshoff Pol, Grant W. Montgomery, Roel A. Ophoff, Markus M. Nöthen, Sara Pudas, Sigurdur Sigurdsson, Arthur W. Toga, Tien Yin Wong, Massimo Pandolfo, Corina U. Greven, Esther Walton, Tianye Jia, David J. Stott, Gunter Schumann, Marie-José van Tol, Dalia Kasperaviciute, Thomas Wolfers, Henry Völzke, Ian Ford, Shannon L. Risacher, Jessika E. Sussmann, Nicholas G. Martin, Wei Wen, Daniah Trabzuni, Iwona Kłoszewska, Kwangsik Nho, Gianpiero L. Cavalleri, Adam M. Brickman, Sungeun Kim, Andreas Heinz, Ralph L. Sacco, Neda Jahanshad, Velandai Srikanth, Elena Shumskaya, Susan H. Blanton, Katharina Wittfeld, Badri N. Vardarajan, Joshua C. Bis, Joanne E. Curran, Helena Schmidt, Peter T. Fox, Clifford R. Jack, Jason L. Stein, Laura M. E. Blanken, Thomas Espeseth, Dick J. Veltman, Sebastian Guelfi, Margaret J. Wright, Norman Delanty, Michael Czisch, Martina Papmeyer, Oscar L. Lopez, Marjolein M. J. Van Donkelaar, Bruce M. Psaty, Jan K. Buitelaar, Sven J. van der Lee, David A. Bennett, Beng-Choon Ho, Oliver Martinez, Wiepke Cahn, Li Shen, J. Wouter Jukema, Janita Bralten, Peter Kochunov, Greig I. Zubicaray, Marcel P. van der Brug, Ching-Yu Cheng, Philipp G. Sämann, Stella Trompet, Roberto Roiz-Santiañez, David C. Glahn, Allissa Dillman, Venkata S. Mattay, Dara M. Cannon, Michael W. Weiner, Christopher D. Whelan, Alexander Teumer, Sylvane Desrivières, Ole A. Andreassen, Thomas E. Nichols, Manuel Mattheisen, Matthias Nauck, René S. Kahn, Albert V. Smith, Colin Smith, Vilmundur Gudnason, Denis A. Evans, Anouk den Braber, Katie L. McMahon, Han G. Brunner, Florian Holsboer, Yuri Milaneschi, Andrew J. Saykin, Jiemin Liao, Vince D. Calhoun, Neelum T. Aggarwal, Dennis van der Meer, Hans J. Grabe, Anita L. DeStefano, Claudia L. Satizabal, Alan B. Zonderman, Alex P. Zijdenbos, Tulio Guadalupe, Ingrid Agartz, Jordan W. Smoller, Allison C. Nugent, Alejandro Arias-Vasquez, Masashi Ikeda, Avram J. Holmes, Brenda W.J.H. Penninx, John Hardy, Herve Lemaitre, Charles DeCarli, Patrizia Mecocci, Catharina A. Hartman, Tomas Axelsson, Oliver Grimm, Irina Filippi, Wayne C. Drevets, Hans van Bokhoven, Miguel E. Rentería, Aiden Corvin, Ryota Kanai, Kristel R. van Eijk, Andrew M. McIntosh, Jouke-Jan Hottenga, Roberto Toro, Lavinia Athanasiu, Joanna M. Wardlaw, Thomas H. Mosley, Mina Ryten, Meike W. Vernooij, Michelle Luciano, Joshua L. Roffman, Rebecca F. Gottesman, Dhananjay Vaidya, Ryota Hashimoto, Mar Matarin, Adaikalavan Ramasamy, Jerome I. Rotter, Ryan L. Muetzel, Konstantinos Arfanakis, Theo G.M. van Erp, Ganesh Chauhan, Xinmin Liu, Tomáš Paus, Emma Sprooten, Christiane Wolf, David S. Knopman, Manon Bernard, Zdenka Pausova, Bryan J. Traynor, Maria C. Valdés Hernández, Robert C. Green, Russell Thomson, Ravi Duggirala, Lisa R. Yanek, Luigi Ferrucci, Bing Xu, Thomas D. Dyer, Thomas H. Wassink, Eric Westman, Jennifer S. Richards, Phil H. Lee, Benno Pütz, Mark R. Cookson, Benedicto Crespo-Facorro, Natalie A. Royle, Bernd Kraemer, Katrin Hegenscheid, Francis J. McMahon, Tatiana Foroud, M. Kamran Ikram, Myriam Fornage, Nanda Rommelse, Saima Hilal, Perminder S. Sachdev, Qiang Chen, Najaf Amin, Lenore J. Launer, Norbert Hosten, Guillén Fernández, Simone Reppermund, Ashley Beecham, Dirk J. Heslenfeld, Masaki Fukunaga, Cornelia M. van Duijn, Clinton B. Wright, Erik G. Jönsson, Sanjay M. Sisodiya, Oliver Gruber, Christophe Tzourio, André G. Uitterlinden, Robert Johnson, Jaap Oosterlaan, Bernard Mazoyer, H. Ronald Zielke, Stephanie Le Hellard, Jingyun Yang, Georg Homuth, Stéphanie Debette, Nicola J. Armstrong, Sarah E. Medland, Henry Brodaty, Beverly G Windham, Gary Donohoe, Rachel M. Brouwer, James T. Becker, Kumar B. Rajan, Daan van Rooij, Thomas W. Mühleisen, Kazutaka Ohi, Peter R. Schofield, Tonya White, Barbara Franke, Unn K. Haukvik, Debra A. Fleischman, J. Raphael Gibbs, Colm McDonald, Anbupalam Thalamuthu, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Keck School of Medicine [Los Angeles], University of Southern California (USC), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Johns Hopkins University (JHU), QIMR Berghofer Medical Research Institute, Leiden University Medical Center (LUMC), Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University of Miami Leonard M. Miller School of Medicine (UMMSM), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, Department of Neurology and Neurosurgery [Montreal], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Royal College of Surgeons in Ireland (RCSI), Umeå University, Illinois Institute of Technology (IIT), Rush University Medical Center [Chicago], University of Edinburgh, Lagos State University (LASU), University of New South Wales [Sydney] (UNSW), Murdoch University, University of Oslo (UiO), Uppsala University, Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Toronto, University of Washington [Seattle], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Columbia University Medical Center (CUMC), Columbia University [New York], Pennington Biomedical Research Center, Louisiana State University (LSU), McGill University = Université McGill [Montréal, Canada], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lieber Institute for Brain Development [Baltimore] (LIBD), University of California [Los Angeles] (UCLA), University of California, Vrije Universiteit Amsterdam [Amsterdam] (VU), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Massachusetts General Hospital [Boston], Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Maison de Solenn [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Bergen (UiB), Haukeland University Hospital, Johns Hopkins University School of Medicine [Baltimore], Universität Heidelberg [Heidelberg], University of Mississippi Medical Center (UMMC), International Max Planck Research School for Language Sciences (IMPRS ), Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Language and Genetics Department [Nijmegen], National University of Singapore (NUS), Medical University Graz, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Yale University [New Haven], University College of London [London] (UCL), Imperial College London, Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Medstar Research Institute, Clinical And Experimental Epilepsy, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], Institute of Human Genetics, University of Bonn, Department of Genomics, Life and Brain Center, Groupe d'imagerie neurofonctionnelle (GIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Dpt of Psychiatry [New Haven], Yale University School of Medicine, Department of Psychiatry, VU University Medical Center [Amsterdam], Department of Psychology [Minneapolis], University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Indiana University System, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Statistical Genetics Group, Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), INSERM, Neuroepidemiology U708, Bordeaux, France, Department of Cognitive Sciences [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, Department of Neurosciences [San Diego], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Queensland Institute of Medical Research, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics, King Faisal Specialist Hospital and Research Centre, Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Depts of Radiology, University of Twente [Netherlands], Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Deutsche Bundesbank, National Institutes of Health [Bethesda] (NIH), General Internal Medicine, Johns Hopkins School of Medicine, Biospective [Montréal], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Department of Clinical Genetics, Department of Medical Parasitology and Mycology, School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-Tehran University of Medical Siences, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The University of Texas Health Science Center at Houston (UTHealth), Texas Biomedical Research Institute [San Antonio, TX], 849 Department of Human Genetics, Dementia Collaborative Research Centre, Centre for Healthy Brain Ageing, Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Université de Lausanne (UNIL), Department of Psychiatry [Boston], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Division of Molecular and Cellular Therapeutics, Metacohorts Consortium, Division of Medical Genetics, University of Basel (Unibas), Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Trinity College Dublin-St. James's Hospital, Department of Materials Science & Metallurgy, University of Cambridge [UK] (CAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], VU University Amsterdam, Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), School of Psychology, University of Queensland, Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Molecular and Cellular Therapeutics, Department of Neurology, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratory of Neurogenetics, Department of Genomics, Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Department of Radiology, Mayo Clinic, Department of Medical and Molecular Genetics, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, Department of Physics, Okayama University, Okayama University, National Institute of Aging, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Public Health Genomics Unit, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Department of Mathematics, University of Colorado, University of Colorado [Boulder], Icelandic Heart Association, Kopavogur, Iceland., Faculty of Medicine, University of Iceland [Reykjavik], Department of Molecular Neurosciences, Institute of Neurology, UCL, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University [Osaka], Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Tohoku University [Sendai], Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Centre for Allergy Research, Karolinska Institutet [Stockholm], Interuniversity Cardiology Institute Netherlands, Institute of Cognitive Neuroscience, School of Psychology, University of Sussex, Brighton BN1 9QH, UK, University of Sussex, Medical University of Łódź (MUL), Mayo Clinic [Rochester], University of Maryland School of Medicine, University of Maryland System-University of Maryland System-University of Maryland [Baltimore County] (UMBC), University of Maryland System, Department of Civil and Structural Engineering, The Hong Kong Polytechnic University [Hong Kong] (POLYU)-The Hong Kong Polytechnic University [Hong Kong] (POLYU), Université de Cergy Pontoise (UCP), Université Paris-Seine, Lymphocyte Cell Biology Unit, Laboratory of Genetics, Laboratoire de Statistique Théorique et Appliquée (LSTA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Psychiatry Institute, Department of Health and Human Services, Department of Life Sciences, Mathematical Sciences Institute (MSI), Australian National University (ANU), Centre for Advanced Imaging, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia (UNIPG), Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Medical Faculty [Mannheim], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, Université de Toulon - UFR Lettres et Sciences Humaines (UTLN UFR LSH), Université de Toulon (UTLN), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Institute of Clinical Chemistry and Laboratory Medicine, Warwick Manufacturing Group [Coventry] (WMG), University of Warwick [Coventry], Department of Statistics [Warwick], Delft University of Technology (TU Delft), Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre (MNI), Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, Group Health Research Institute, Group Health Cooperative, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Cedars-Sinai Medical Center, Centre for Healthy Brain Ageing [Sydney], The University of Sydney, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Department of Medical Biochemistry and Microbiology, Department of Clinical and Experimental Epilepsy, Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Monash University [Melbourne], Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia, University of Tasmania [Hobart, Australia] (UTAS), Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Department of Epidemiology, Laboratory of Neuro Imaging [Los Angeles] (LONI), University of York [York, UK], Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Genentech, Inc. [San Francisco], Departments of Radiology and of Epidemiology [Rotterdam], Psychiatry and Leiden Institute for Brain and Cognition, Department of Neurology [Rotterdam], Institute for Community Medicine, Berlin School of Mind and Brain [Berlin], Humboldt-Universität zu Berlin, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Centre for Population Health Sciences, Department of Physics [Hong Kong University of Science and Technology], Hong Kong University of Science and Technology (HKUST), Department of Neurobiology, Care Sciences and Society, Research Laboratory for Archaeology & the History of Art, Singapore Eye Research Institute, Singapore National Eye Centre, School of Life Sciences, Arizona State University [Tempe] (ASU), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), Dpt of Pharmacology and Personalised Medicine [Maastricht], Maastricht University [Maastricht], University of Missouri [Columbia] (Mizzou), University of Missouri System, Göttingen Zentrum Geowissenschaften, Georg-August-University [Göttingen], Human Genetics Center, Psychiatry, EMGO - Mental health, Amsterdam Neuroscience - Complex Trait Genetics, Anatomy and neurosciences, Klinische Genetica, MUMC+: DA Klinische Genetica (5), RS: FHML non-thematic output, RS: GROW - School for Oncology and Reproduction, RS: GROW - R4 - Reproductive and Perinatal Medicine, Genetica & Celbiologie, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Universidad de Cantabria, Universiteit Leiden, Radboud University [Nijmegen], University of California (UC), Universität Heidelberg [Heidelberg] = Heidelberg University, Universität Bonn = University of Bonn, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Yale School of Medicine [New Haven, Connecticut] (YSM), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), University of California (UC)-University of California (UC), Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), King Faisal Specialist Hospital and Research Centre (KFSH & RC), Universiteit Leiden-Universiteit Leiden, University of Twente, University of California [Irvine] (UC Irvine), Radboud University [Nijmegen]-Radboud University [Nijmegen], Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Università degli Studi di Perugia = University of Perugia (UNIPG), University Hospital Mannheim | Universitätsmedizin Mannheim, Universität Leipzig-Universität Leipzig, University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, Harvard University-Massachusetts Institute of Technology (MIT), University of Eastern Finland, Humboldt University Of Berlin, Georg-August-University = Georg-August-Universität Göttingen, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Epidemiology, Child and Adolescent Psychiatry / Psychology, Ophthalmology, Radiology & Nuclear Medicine, Internal Medicine, Neurosciences, Obstetrics & Gynecology, Neurology, EMGO+ - Mental Health, Biological Psychology, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), McGill University-McGill University, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), McGill University, Technische Universität Dresden (TUD), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], University of Bergen (UIB), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Minnesota [Twin Cities], Karakter Child and Adolescent Psychiatry University Center Nijmegen, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Okayama University [Okayama], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], University of Tasmania (UTAS), Humboldt Universität zu Berlin, Department of Physics [Kowloon], University of Missouri [Columbia], Georg-August-Universität Göttingen, and the Alzheimer's Disease Neuroimaging Initiative, EPIGEN, IMAGEN, SYS
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Genome-wide association study, Disease, methods [Genome-Wide Association Study], Genome-wide association studies, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Cognition, PARKINSONS-DISEASE, pathology [Brain], genetics [Parkinson Disease], 610 Medicine & health, General Neuroscience, growth & development [Brain], physiology [Cognition], 220 Statistical Imaging Neuroscience, COMMON VARIANTS, Brain, Parkinson Disease, Phenotype, 17Q21.31 MICRODELETION, IGF-I, genetics [Oncogene Protein v-akt], Oncogene Protein v-akt, ALZHEIMERS-DISEASE, HEAD CIRCUMFERENCE, Brain size, genetics [Polymorphism, Single Nucleotide], Medical genetics, GROWTH, Neuroinformatics, medicine.medical_specialty, Neuroscience(all), European Continental Ancestry Group, genetics [Genetic Loci], Biology, Genetic correlation, Polymorphism, Single Nucleotide, 150 000 MR Techniques in Brain Function, Article, White People, 03 medical and health sciences, Image processing, SDG 3 - Good Health and Well-being, ddc:570, medicine, Journal Article, Humans, Genetic Predisposition to Disease, Gene, METAANALYSIS, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Neurology & Neurosurgery, Neuroscience (all), Height, [SCCO.NEUR]Cognitive science/Neuroscience, CONSORTIUM, Development of the nervous system, 1702 Cognitive Science, 030104 developmental biology, Genetic Loci, Human genome, BRAIN SIZE, 1109 Neurosciences, genetics [Phosphatidylinositol 3-Kinases], Neuroscience, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Contains fulltext : 165723pub.pdf (Publisher’s version ) (Closed access) Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rhogenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
Published: 2016

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

Author: Mar Matarin, Douglas N. Greve, Nic J.A. van der Wee, Evan Fletcher, Christiane Wolf, Arvin Saremi, Joshua W. Cheung, Randy L. Gollub, David Ames, Honghuang Lin, Nicholas G. Martin, Manon Bernard, Daniel R. Weinberger, Henry Völzke, Manuel Mattheisen, George Davey Smith, Dan J. Stein, Dorret I. Boomsma, John D. Eicher, Henrik Walter, Massimo Pandolfo, Andreas Meyer-Lindenberg, D. Hoehn, Louis N. Vinke, Wiro J. Niessen, G. Bruce Pike, Simon E. Fisher, Jerome I. Rotter, Neeltje E.M. van Haren, Neda Jahanshad, Stephen M. Lawrie, Mark E. Bastin, Sanjay M. Sisodiya, Marcella Rietschel, Jean Shin, Dirk J. Heslenfeld, Ingrid Agartz, Lars Nyberg, Nina Romanczuk-Seiferth, Clifford R. Jack, Markus Scholz, Baljeet Singh, Rachel M. Brouwer, Marco P. Boks, M. Mallar Chakravarty, Magda Tsolaki, André G. Uitterlinden, Amelia A. Assareh, Nastassja Koen, Beng-Choon Ho, Muralidharan Sargurupremraj, Perminder S. Sachdev, James T. Becker, Narelle K. Hansell, Katrin Hegenscheid, Zdenka Pausova, Irina Filippi, Hans van Bokhoven, Miguel E. Rentería, Robert C. Green, M. Kamran Ikram, Vidar M. Steen, Marc M. Bohlken, Iryna O. Fedko, Jayandra J. Himali, Hieab H.H. Adams, Erik G. Jönsson, Esther Walton, Gunter Schumann, Dennis van der Meer, Jordan W. Smoller, Ganesh Chauhan, Simon Lovestone, Kwangsik Nho, Gianpiero L. Cavalleri, Andrew Simmons, Shuo Li, Hannah J. Jones, Lavinia Athanasiu, Shahrzad Kharabian Masouleh, Micael Andersson, Andreas Heinz, Lucija Abramovic, Alexa S. Beiser, Vilmundur Gudnason, Oliver Gruber, Tianye Jia, Daan van Rooij, Philip L. De Jager, Allison Stevens, Thomas W. Mühleisen, Deborah Janowitz, Anita L. DeStefano, Gennady V. Roshchupkin, Maria C. Valdés Hernández, Nynke A. Groenewold, Vince D. Calhoun, Cornelia M. van Duijn, Roberto Toro, Wiepke Cahn, Florian Holsboer, Asta Håberg, Aaron Goldman, Lisa R. Yanek, Jingyun Yang, Matthias L. Schroeter, Patrizia Mecocci, Sven J. van der Lee, Gareth E. Davies, Elena Shumskaya, Jia Yu Koh, Thomas H. Wassink, Wei Wen, A. Veronica Witte, Anders M. Dale, Diana Tordesillas-Gutiérrez, Iwona Kłoszewska, Benedicto Crespo-Facorro, Sylvane Desrivières, Catharina A. Hartman, Saskia P. Hagenaars, Jennifer S. Richards, Martine Hoogman, Philipp G. Sämann, Andre F. Marquand, Stephanie Le Hellard, Christophe Tzourio, Sven Cichon, Tomáš Paus, Ole A. Andreassen, Pieter J. Hoekstra, Gabriel Cuellar-Partida, Joanna M. Wardlaw, Thomas H. Mosley, Bernd Kraemer, Barbara Franke, Joshua C. Bis, Katharina Wittfeld, Christopher D. Whelan, Christine Macare, Unn K. Haukvik, Lars T. Westlye, Loes M. Olde Loohuis, Sudha Seshadri, Michelle Luciano, Shannon L. Risacher, Diane M. Becker, Tamara B. Harris, Georg Homuth, Sungeun Kim, Lenore J. Launer, Debra A. Fleischman, Tulio Guadalupe, Joshua L. Roffman, Marie-José van Tol, Stéphanie Debette, Benno Pütz, Dick J. Veltman, Ching-Yu Cheng, Norman Delanty, Chantal Depondt, Jaap Oosterlaan, Nicola J. Armstrong, Myriam Fornage, Eric Westman, Anouk den Braber, Nanda Rommelse, Qiong Yang, Yasaman Saba, Tatiana Foroud, Susanne Erk, Saima Hilal, Paul M. Thompson, Eco J. C. de Geus, Paul A. Nyquist, Wolfgang Hoffmann, Alexander Teumer, Avram J. Holmes, Qiang Chen, Najaf Amin, Albert V. Smith, Tom V. Lee, Sarah E. Medland, Nazanin Mirza-Schreiber, Alejandro Arias-Vasquez, Grant W. Montgomery, Han G. Brunner, Meike W. Vernooij, Bernard Mazoyer, Guillén Fernández, Henry Brodaty, Claudia L. Satizabal, Thomas Wolfers, Herve Lemaitre, Li Shen, Greig I. de Zubicaray, Pauline Maillard, Hans J. Grabe, Ingrid Melle, Simone Reppermund, Charles DeCarli, Anbupalam Thalamuthu, Helena Schmidt, Peter R. Schofield, Marjolein M.J. van Donkelaar, Thomas Espeseth, Christopher Chen, Matthias Nauck, Norbert Hosten, Clyde Francks, Oliver Grimm, Tonya White, Andrew J. Saykin, Andrew M. McIntosh, Oscar L. Lopez, Philippe Amouyel, William T. Longstreth, Janita Bralten, Nhat Trung Doan, John B.J. Kwok, Charles C. White, Ralph Burkhardt, Jessika E. Sussmann, Michael W. Weiner, Markus M. Nöthen, Katie L. McMahon, Derrek P. Hibar, Dalia Kasperaviciute, Maria J. Knol, Hilleke E. Hulshoff Pol, Markus Loeffler, Bruno Vellas, Matthew J. Huentelman, Owen Carmichael, Jason L. Stein, Ryota Kanai, Lianne Schmaal, Hilkka Soininen, Bruce M. Psaty, Jan K. Buitelaar, Jean-Luc Martinot, Ian J. Deary, Venkata S. Mattay, Theo G.M. van Erp, Arno Villringer, Andrew D. Johnson, Srdjan Djurovic, Benjamin S. Aribisala, Lachlan T. Strike, Phil Lee, David C. Liewald, Tien Yin Wong, Tomas Axelsson, Jessica A. Turner, Marieke Klein, Kristel R. van Eijk, Saud Alhusaini, Konstantinos Arfanakis, M. Arfan Ikram, Stefan Ehrlich, Sebastian Mohnke, Marcel P. Zwiers, Karen A. Mather, Jonathan C Ipser, Joshua M. Shulman, Brenda W.J.H. Penninx, Reinhold Schmidt, Arthur W. Toga, Christopher R.K. Ching, René S. Kahn, Bertram Müller-Myhsok, Yuri Milaneschi, Margaret J. Wright, Martina Papmeyer, Fabrice Crivello, David A. Bennett, Randy L. Buckner, Edith Hofer, Roel A. Ophoff, Steven G. Potkin, Albert Hofman, Dennis van 't Ent, Sudheer Giddaluru, Roberto Roiz-Santiañez, Andrew J. Schork, Jouke-Jan Hottenga, Yanhui Hu, Kazima B. Bulayeva, Xueqiu Jian, Clinical Genetics, Epidemiology, Radiology & Nuclear Medicine, Medical Informatics, Neurology, Child and Adolescent Psychiatry / Psychology, Psychiatry, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), APH - Mental Health, Pediatric surgery, Epidemiology and Data Science, Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, APH - Digital Health, General Paediatrics, ARD - Amsterdam Reproduction and Development, Psychiatrie & Neuropsychologie, Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), RS: MHeNs - R2 - Mental Health, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Stochastics, Biological Psychology, APH - Methodology, Clinical Neuropsychology, IBBA, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, and Cognitive Psychology
Subjects: Netherlands Twin Register (NTR), LD SCORE REGRESSION, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Caudate nucleus, Genome-wide association study, Bio-Organic Chemistry, Language in Interaction, neuroscience, Cohort Studies, BASAL GANGLIA, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, metabolism [Drosophila melanogaster], Basal ganglia, Adult, Aged, Animals, Brain, Drosophila melanogaster, Humans, Magnetic Resonance Imaging, Middle Aged, Neurodevelopmental Disorders, Organ Size, Genetic Variation, Genome-Wide Association Study, genetics [Drosophila melanogaster], 0303 health sciences, genetics [Neurodevelopmental Disorders], Putamen, 220 Statistical Imaging Neuroscience, 3. Good health, ALZHEIMERS-DISEASE, DROSOPHILA, Globus pallidus, VINTAGE, epidemiology, Synaptic signaling, Neuroinformatics, EXPRESSION, Nucleus accumbens, Biology, 150 000 MR Techniques in Brain Function, Article, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, ddc:570, PLASMA-PROTEIN, pathology [Neurodevelopmental Disorders], Genetics, GENOME-WIDE ASSOCIATION, HEALTHY, METAANALYSIS, 030304 developmental biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], RISK LOCI, Genetic architecture, ALKALINE-PHOSPHATASE, nervous system, metabolism [Brain], genome-wide association studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, growth & development [Drosophila melanogaster], anatomy & histology [Brain], Neuroscience, 030217 neurology & neurosurgery
Abstract: Aims/hypothesis MODY can be wrongly diagnosed as type 1 diabetes in children. We aimed to find the prevalence of MODY in a nationwide population-based registry of childhood diabetes. Methods Using next-generation sequencing, we screened the HNF1A, HNF4A, HNF1B, GCK and INS genes in all 469 children (12.1%) negative for both GAD and IA-2 autoantibodies and 469 antibody-positive matched controls selected from the Norwegian Childhood Diabetes Registry (3882 children). Variants were classified using clinical diagnostic criteria for pathogenicity ranging from class 1 (neutral) to class 5 (pathogenic). Results We identified 58 rare exonic and splice variants in cases and controls. Among antibody-negative patients, 6.5% had genetic variants of classes 3–5 (vs 2.4% in controls; p = 0.002). For the stricter classification (classes 4 and 5), the corresponding number was 4.1% (vs 0.2% in controls; p = 1.6 × 10−5). HNF1A showed the strongest enrichment of class 3–5 variants, with 3.9% among antibody-negative patients (vs 0.4% in controls; p = 0.0002). Antibody-negative carriers of variants in class 3 had a similar phenotype to those carrying variants in classes 4 and 5. Conclusions/interpretation This is the first study screening for MODY in all antibody-negative children in a nationwide population-based registry. Our results suggest that the prevalence of MODY in antibody-negative childhood diabetes may reach 6.5%. One-third of these MODY cases had not been recognised by clinicians. Since a precise diagnosis is important for treatment and genetic counselling, molecular screening of all antibody-negative children should be considered in routine diagnostics.
Published: 2019

44. Heritability of Resting State EEG Functional Connectivity Patterns

Author: Dirk J.A. Smit, Nicholas G. Martin, Eco J. C. de Geus, Margaret J. Wright, Nienke M. Schutte, Narelle K. Hansell, Biological Psychology, and Neuroscience Campus Amsterdam - Neurobiology of Mental Health
Subjects: Power graph analysis, Brain Mapping, Communication, medicine.diagnostic_test, Resting state fMRI, business.industry, Brain, Obstetrics and Gynecology, Electroencephalography, Heritability, Brain mapping, Twin study, Average path length, Phenotype, Path length, Pediatrics, Perinatology and Child Health, Statistics, Twins, Dizygotic, medicine, Humans, Psychology, business, Genetics (clinical)
Abstract: We examined the genetic architecture of functional brain connectivity measures in resting state electroencephalographic (EEG) recordings. Previous studies in Dutch twins have suggested that genetic factors are a main source of variance in functional brain connectivity derived from EEG recordings. In addition, qualitative descriptors of the brain network derived from graph analysis — network clustering and average path length — are also heritable traits. Here we replicated previous findings for connectivity, quantified by the synchronization likelihood, and the graph theoretical parameters cluster coefficient and path length in an Australian sample of 16-year-old twins (879) and their siblings (93). Modeling of monozygotic and dizygotic twins and sibling resemblance indicated heritability estimates of the synchronization likelihood (27–74%) and cluster coefficient and path length in the alpha and theta band (40–44% and 23–40% respectively) and path length in the beta band frequency (41%). This corroborates synchronization likelihood and its graph theoretical derivatives cluster coefficient and path length as potential endophenotypes for behavioral traits and neurological disorders.
Published: 2013

45. The relationship of reading ability to creativity: Positive, not negative associations

Author: Margaret J. Wright, Michelle Luciano, Timothy C. Bates, Narelle K. Hansell, and Stuart J. Ritchie
Subjects: Reading disability, Social Psychology, media_common.quotation_subject, Dyslexia, Creativity, medicine.disease, Spelling, Education, Developmental psychology, Reading (process), Learning disability, Developmental and Educational Psychology, Trait, medicine, Openness to experience, medicine.symptom, Psychology, media_common, Cognitive psychology
Abstract: It has been argued that reading disability may be accompanied by compensatory enhancements in creativity. Here, we assessed reading, spelling and nonword repetition in a large, representative sample of adolescents and young adults, and examined associations with creativity, indexed by trait Openness to Experience and a creative writing task. Creativity and reading ability were significantly associated in a series of regression models controlling for IQ, age, and sex, but the effect was in the opposite direction to that predicted by compensation hypotheses: Higher reading scores were associated with higher scores on creativity measures. We discuss possible explanations for this finding, suggesting a ‘facilitation’ hypothesis by which reading ability might facilitate creative thinking.
Published: 2013

46. A genome‐wide association study for reading and language abilities in two population cohorts

Author: Timothy C. Bates, David M. Evans, Nicholas G. Martin, Margaret J. Wright, Narelle K. Hansell, Michelle Luciano, Sarah E. Medland, and Grant W. Montgomery
Subjects: Male, Longitudinal study, Candidate gene, Twins, Genome-wide association study, Dyslexia, Behavioral Neuroscience, 0302 clinical medicine, GWAS, Language disorder, genes, Child, Genetics, 0303 health sciences, education.field_of_study, Language Tests, RNA-Binding Proteins, Cyclin-Dependent Kinases, Neurology, Chromosomes, Human, Pair 1, Cohort, Female, Psychology, Pseudogenes, Adult, Adolescent, Population, Single-nucleotide polymorphism, Language Development, Polymorphism, Single Nucleotide, Association, 03 medical and health sciences, reading, medicine, Humans, education, Adaptor Proteins, Signal Transducing, 030304 developmental biology, language, Siblings, Original Articles, medicine.disease, Genetic Loci, Case-Control Studies, ATP-Binding Cassette Transporters, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Candidate genes have been identified for both reading and language, but most of the heritable variance in these traits remains unexplained. Here, we report a genome-wide association meta-analysis of two large cohorts: population samples of Australian twins and siblings aged 12-25 years (n = 1177 from 538 families), and a younger cohort of children of the UK Avon Longitudinal Study of Parents and their Children (aged 8 and 9 years; maximum n = 5472). Suggestive association was indicated for reading measures and non-word repetition (NWR), with the greatest support found for single nucleotide polymorphisms (SNPs) in the pseudogene, ABCC13 (P = 7.34 × 10(-8)), and the gene, DAZAP1 (P = 1.32 × 10(-6)). Gene-based analyses showed significant association (P 2.8 × 10(-6)) for reading and spelling with genes CD2L1, CDC2L2 and RCAN3 in two loci on chromosome 1. Some support was found for the same SNPs having effects on both reading skill and NWR, which is compatible with behavior genetic evidence for influences of reading acquisition on phonological-task performance. The results implicate novel candidates for study in additional cohorts for reading and language abilities.
Published: 2013

47. A commonly carried genetic variant in the delta opioid receptor gene,OPRD1,is associated with smaller regional brain volumes: Replication in elderly and young populations

Author: Nicholas G. Martin, Clifford R. Jack, Paul M. Thompson, Greig I. de Zubicaray, Grant W. Montgomery, Derrek P. Hibar, Michael Weiner, Narelle K. Hansell, Arthur W. Toga, Margaret J. Wright, Neda Jahanshad, Elizabeth R. Sowell, Katie L. McMahon, Marina Barysheva, Florence F. Roussotte, and Omid Kohannim
Subjects: Radiological and Ultrasound Technology, Addiction, media_common.quotation_subject, Disease, Bioinformatics, medicine.disease, δ-opioid receptor, Neurology, Opioid, Neuroimaging, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Anatomy, Allele, Alzheimer's disease, Receptor, Psychology, Neuroscience, media_common, medicine.drug
Abstract: Delta opioid receptors are implicated in a variety of psychiatric and neurological disorders. These receptors play a key role in the reinforcing properties of drugs of abuse, and polymorphisms in OPRD1 (the gene encoding delta opioid receptors) are associated with drug addiction. Delta opioid receptors are also involved in protecting neurons against hypoxic and ischemic stress. Here, we first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative. We hypothesized that common variants in OPRD1 would be associated with differences in brain structure, particularly in regions relevant to addictive and neurodegenerative disorders. One very common variant (rs678849) predicted differences in regional brain volumes. We replicated the association of this single-nucleotide polymorphism with regional tissue volumes in a large sample of young participants in the Queensland Twin Imaging study. Although the same allele was associated with reduced volumes in both cohorts, the brain regions affected differed between the two samples. In healthy elderly, exploratory analyses suggested that the genotype associated with reduced brain volumes in both cohorts may also predict cerebrospinal fluid levels of neurodegenerative biomarkers, but this requires confirmation. If opiate receptor genetic variants are related to individual differences in brain structure, genotyping of these variants may be helpful when designing clinical trials targeting delta opioid receptors to treat neurological disorders.
Published: 2013

48. No Association Between General Cognitive Ability and Rare Copy Number Variation

Author: Nicholas G. Martin, Allan F. McRae, Narelle K. Hansell, Margaret J. Wright, and Grant W. Montgomery
Subjects: Adult, Male, Adolescent, DNA Copy Number Variations, genetic structures, Intelligence, Gene Dosage, Genome-wide association study, Polymorphism, Single Nucleotide, Correlation, Young Adult, Cognition, Polymorphism (computer science), Genetics, Humans, Copy-number variation, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Intelligence Tests, Intelligence quotient, Twin study, eye diseases, SNP genotyping, Female, sense organs, Psychology, Genome-Wide Association Study
Abstract: There is increasing evidence for the role of rare copy-number variation (CNV) in the development of neuropsychiatric disorders. It is likely that such variants also have an effect on the variation of cognition in what is considered the “normal” phenotypic range. The role of rare CNV (>20 KB in length; frequency
Published: 2013

49. A study of changes in genetic and environmental influences on weight and shape concern across adolescence

Author: Narelle K. Hansell, Rachel Bryant-Waugh, Janet Treasure, Tracey D. Wade, Ross D. Crosby, Susan M. Byrne, Reginald D. V. Nixon, and Nicholas G. Martin
Subjects: Longitudinal study, Multivariate analysis, Adolescent, Twins, Environmental, Developmental psychology, Feeding and Eating Disorders, Genetic, Risk Factors, Surveys and Questionnaires, Weight and shape concern, Body Image, medicine, Body Size, Humans, Longitudinal Studies, Gene–environment interaction, Disordered eating, Risk factor, Child, Biological Psychiatry, Body Weight, Variance (accounting), medicine.disease, Clinical Psychology, Psychiatry and Mental health, Eating disorders, Multivariate Analysis, Cohort, Female, Gene-Environment Interaction, Psychology
Abstract: The goal of the current study was to examine whether genetic and environmental influences on an important risk factor for disordered eating, weight and shape concern (WSC), remained stable over adolescence. This stability was assessed in two ways: whether new sources of latent variance were introduced over development, and whether the magnitude of variance contributing to the risk factor changed. We examined an 8-item WSC sub-scale derived from the Eating Disorder Examination using telephone interviews with female adolescents. From three waves of data collected from female-female same sex twin pairs from the Australian Twin Registry, a subset of the data (which included 351 pairs at Wave 1) was used to examine three age cohorts: 12-13, 13-15, and 14-16 years. The best fitting model contained genetic and environmental influences, both shared and non-shared. Biometric model fitting indicated that non-shared environmental influences were largely specific to each age cohort, and results suggested that latent shared environmental and genetic influences that were influential at 12-13 years continued to contribute to subsequent age cohorts, with independent sources of both emerging at ages 13-15. The magnitude of all three latent influences could be constrained to be the same across adolescence. Ages 13-15 was indicated as a time of risk for the development of high levels of WSC given that most specific environmental risk factors were significant at this time (e.g., peer teasing about weight, adverse life events), and indications of the emergence of new sources of latent genetic and environmental variance over this period., NHMRC Grants 324715 and 480420.
Published: 2013

50. Genome-wide association study of working memory brain activation

Author: Paul M. Thompson, Nicholas G. Martin, Grant W. Montgomery, Ian B. Hickie, Greig I. de Zubicaray, Angus K. Wallace, Narelle K. Hansell, Margaret J. Wright, Katie L. McMahon, and Gabriëlla A.M. Blokland
Subjects: 0301 basic medicine, Adult, Male, Linkage disequilibrium, Adolescent, Genotype, Population, Twins, Single-nucleotide polymorphism, Genome-wide association study, Neuropsychological Tests, Polymorphism, Single Nucleotide, Article, Community Health Planning, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Region of interest, Physiology (medical), Image Processing, Computer-Assisted, Humans, education, Genetics, n-back, Communication, education.field_of_study, Models, Genetic, business.industry, Working memory, General Neuroscience, Brain, Reproducibility of Results, Heritability, Magnetic Resonance Imaging, Oxygen, 030104 developmental biology, Neuropsychology and Physiological Psychology, Memory, Short-Term, Phenotype, Female, business, Psychology, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: In a population-based genome-wide association (GWA) study of n-back working memory task-related brain activation, we extracted the average percent BOLD signal change (2-back minus 0-back) from 46 regions-of-interest (ROIs) in functional MRI scans from 863 healthy twins and siblings. ROIs were obtained by creating spheres around group random effects analysis local maxima, and by thresholding a voxel-based heritability map of working memory brain activation at 50%. Quality control for test-retest reliability and heritability of ROI measures yielded 20 reliable (r>0.7) and heritable (h2>20%) ROIs. For GWA analysis, the cohort was divided into a discovery (n=679) and replication (n=97) sample. No variants survived the stringent multiple-testing-corrected genome-wide significance threshold (p
Published: 2016

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