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Identification of common variants associated with human hippocampal and intracranial volumes

Jason Stein 1 Sarah Medland 2 Alejandro Vasquez 3 Derrek Hibar 1 Rudy Senstad 1 Anderson Winkler 4 Roberto Toro 5 Katja Appel 6, 7 Richard Bartecek 8 Ørjan Bergmann 9 Manon Bernard 10 Andrew Brown 9 Dara Cannon 11 M Mallar Chakravarty 12 Andrea Christoforou 13 Martin Domin 6 Oliver Grimm 7 Marisa Hollinshead 14 Avram Holmes 14 Georg Homuth 6 Jouke-Jan Hottenga 15 Camilla Langan 11 Lorna Lopez 16 Narelle Hansell 2 Kristy Hwang 1 Sungeun Kim 17 Gonzalo Laje Phil Lee 18 Xinmin Liu 19 Eva Loth 20 Anbarasu Lourdusamy 21 Morten Mattingsdal 9 Sebastian Mohnke Susana Maniega 16 Kwangsik Nho 1 Allison Nugent Carol O'brien Martina Papmeyer Benno Pütz Adaikalavan Ramasamy Jerod Rasmussen Mark Rijpkema 3 Shannon Risacher 1 J Cooper Roddey Emma Rose Mina Ryten Li Shen 1 Emma Sprooten Eric Strengman Alexander Teumer 6 Daniah Trabzuni Jessica Turner 22 Kristel van Eijk 8 Theo van Erp 23 Marie-Jose van Tol 24 Katharina Wittfeld 6 Christiane Wolf 25 Saskia Woudstra Andre Aleman 26 Saud Alhusaini 27 Laura Almasy 28 Elisabeth Binder David Brohawn Rita Cantor Melanie Carless Aiden Corvin Michael Czisch 29 Joanne Curran Gail Davies 16 Marcio de Almeida Norman Delanty 30 Chantal Depondt Ravi Duggirala Thomas Dyer 31 Susanne Erk Jesen Fagerness Peter Fox 31 Nelson Freimer 32 Michael Gill Harald Göring Donald Hagler David Hoehn 33 Florian Holsboer Martine Hoogman 3 Norbert Hosten 6 Neda Jahanshad Matthew Johnson 34 Dalia Kasperaviciute Jack Kent 28 Peter Kochunov Jack Lancaster Stephen Lawrie David Liewald 16 René Mandl 8 Mar Matarin Manuel Mattheisen Eva Meisenzahl Ingrid Melle 9 Eric Moses Thomas Mühleisen Matthias Nauck Markus Nöthen Rene Olvera Massimo Pandolfo G Bruce Pike Ralf Puls 6 Ivar Reinvang Miguel Rentería 2 Marcella Rietschel 7 Joshua Roffman Natalie Royle 16 Dan Rujescu Jonathan Savitz Hugo Schnack 8 Knut Schnell Nina Seiferth Colin Smith 35 Vidar Steen 13 Maria Valdés Hernández 16 Martijn van den Heuvel 8 Nic van der Wee Neeltje van Haren 8 Joris Veltman 3 Henry Völzke Robert Walker Lars Westlye Christopher Whelan Ingrid Agartz 9 Dorret Boomsma 15 Gianpiero Cavalleri Anders Dale Srdjan Djurovic 9 Wayne Drevets Peter Hagoort 3 Jérémy Hall Andreas Heinz 36 Clifford Jack Tatiana Foroud Stephanie Le Hellard 13 Fabio Macciardi 37 Grant Montgomery 2 Jean Poline David Porteous 16 Sanjay Sisodiya 38 John Starr 16 Jessika Sussmann Arthur Toga 1 Dick Veltman Henrik Walter Michael Weiner 39 Joshua Bis 40 M Arfan Ikram 41 Albert Smith 42 Vilmundur Gudnason Christophe Tzourio Meike Vernooij 2 Lenore Launer Charles Decarli Sudha Seshadri Ole Andreassen 9 Liana Apostolova 1 Mark Bastin 16 John Blangero Han Brunner 3 Randy Buckner 14 Sven Cichon Giovanni Coppola 43 Greig de Zubicaray 44 Ian Deary 16 Gary Donohoe Eco de Geus 15 Thomas Espeseth 9 Guillén Fernández 3 David Glahn 45, 4 Hans Grabe 6 John Hardy 46 Hilleke Hulshoff Pol 8 Mark Jenkinson Rene Kahn 8 Colm Mcdonald 11 Andrew Mcintosh Francis Mcmahon Katie Mcmahon 47 Andreas Meyer-Lindenberg 7 Derek Morris Bertram Müller-Myhsok Thomas Nichols Roel Ophoff 8 Tomas Paus 48 Zdenka Pausova 10 Brenda Penninx Steven Potkin Philipp Sämann Andrew Saykin 1 Gunter Schumann 21 Jordan Smoller 49 Joanna Wardlaw 16 Michael Weale Nicholas Martin 2 Barbara Franke 3 Margaret Wright 2 Paul Thompson 1
42 UMR5116
CED - Centre Émile Durkheim
Abstract : Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)).
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Jason Stein, Sarah Medland, Alejandro Vasquez, Derrek Hibar, Rudy Senstad, et al.. Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics, Nature Publishing Group, 2012, 44 (5), pp.552-561. ⟨10.1038/ng.2250⟩. ⟨pasteur-01967151⟩

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