Nature Genetics
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Nature Genetics | Letter
Identification of common variants associated with human hippocampal and intracranial volumes
Jason L Stein,1, 127 Sarah E Medland,2, 3, 4, 127 Alejandro Arias Vasquez,5, 6, 7, 127 Derrek P Hibar,1, 127 Rudy E Senstad,1 Anderson M Winkler,8, 9 Roberto Toro,10, 11, 12 Katja Appel,13, 14 Richard Bartecek,15 ?rjan Bergmann,16 Manon Bernard,17 Andrew A Brown,16, 18 Dara M Cannon,19 M Mallar Chakravarty,21 Andrea Christoforou,22, 23 Martin Domin,24 Oliver Grimm,25 Marisa Hollinshead,26, 27 Avram J Holmes,26 Georg Homuth,28 Jouke-Jan Hottenga,29 Camilla Langan,20 Lorna M Lopez,30, 31 Narelle K Hansell,2 Kristy S Hwang,1, 32
Sungeun Kim,33, 34
Gonzalo Laje,35
Phil H Lee,36, 37
Xinmin Liu,35, 38
Eva Loth,39
Anbarasu Lourdusamy,39
Morten Mattingsdal,16, 40
Sebastian Mohnke,41
Susana Mu?oz Maniega,30, 42, 43
Kwangsik Nho,33, 44
Allison C Nugent,45
Carol O'Brien,46, 47
Martina Papmeyer,48
Benno P?tz,49
Adaikalavan Ramasamy,50
Jerod Rasmussen,51
Mark Rijpkema,7, 52
Shannon L Risacher,33
J Cooper Roddey,53
Emma J Rose,46, 47
Mina Ryten,54
Li Shen,33, 34
Emma Sprooten,48
Eric Strengman,55, 56
Alexander Teumer,28
Daniah Trabzuni,54, 57
Jessica Turner,58
Kristel van Eijk,55, 56
Theo G M van Erp,51
Marie-Jose van Tol,59, 60, 61
Katharina Wittfeld,13
Christiane Wolf,49
Saskia Woudstra,62
Andre Aleman,61
Saud Alhusaini,63
Laura Almasy,64
Elisabeth B Binder,49
David G Brohawn,36
Rita M Cantor,65
Melanie A Carless,64
Aiden Corvin,46, 47
Michael Czisch,49
Joanne E Curran,64
Gail Davies,31
Marcio A A de Almeida,64
Norman Delanty,63, 66
Chantal Depondt,67
Ravi Duggirala,64
Thomas D Dyer,64
Susanne Erk,41
Jesen Fagerness,36
Peter T Fox,69
Nelson B Freimer,65
Michael Gill,46, 47
Harald H H G?ring,64
Donald J Hagler,70
David Hoehn,49
Florian Holsboer,49
Martine Hoogman,5, 7, 71, 72
Norbert Hosten,24
Neda Jahanshad,1
Matthew P Johnson,64
Dalia Kasperaviciute,73
Jack W Kent Jr,64
Peter Kochunov,69, 74
Jack L Lancaster,69
Stephen M Lawrie,48
David C Liewald,30
Ren? Mandl,15
Mar Matarin,73
Manuel Mattheisen,75, 76, 77
Eva Meisenzahl,78
Ingrid Melle,16, 79
Eric K Moses,64
Thomas W M?hleisen,75, 76
Matthias Nauck,80
Markus M N?then,75, 76, 81
Rene L Olvera,82
Massimo Pandolfo,67
G Bruce Pike,83
Ralf Puls,24
Ivar Reinvang,84, 85
Miguel E Renter?a,2, 86
Marcella Rietschel,25
Joshua L Roffman,37
Natalie A Royle,30, 42, 43
Dan Rujescu,78
Jonathan Savitz,45, 87
Hugo G Schnack,15
Knut Schnell,88, 89
Nina Seiferth,41
Colin Smith,90
Vidar M Steen,22, 23
Maria C Vald?s Hern?ndez,30, 42, 43
Martijn Van den Heuvel,15
Nic J van der Wee,59, 60
Neeltje E M Van Haren,15
Joris A Veltman,5
Henry V?lzke,91
Robert Walker,90
Lars T Westlye,84
Christopher D Whelan,63
Ingrid Agartz,16, 92
Dorret I Boomsma,29
Gianpiero L Cavalleri,63
Anders M Dale,53, 70
Srdjan Djurovic,16, 93
Wayne C Drevets,45, 87
Peter Hagoort,7, 52, 72
Jeremy Hall,48
Andreas Heinz,41
Clifford R Jack Jr,94
Tatiana M Foroud,34, 95
Stephanie Le Hellard,22, 23
Fabio Macciardi,51
Grant W Montgomery,2
Jean Baptiste Poline,96
David J Porteous,30, 97
Sanjay M Sisodiya,73
John M Starr,30, 98
Jessika Sussmann,48
Arthur W Toga,1
Dick J Veltman,62
Henrik Walter,41, 89
Michael W Weiner,99, 100, 101, 102
the Alzheimer's Disease Neuroimaging Initiative (ADNI),
EPIGEN Consortium,
IMAGEN Consortium,
Saguenay Youth Study Group (SYS),
Joshua C Bis,104
M Arfan Ikram,105, 106, 107
Albert V Smith,108, 109
Vilmundur Gudnason,108, 109
Christophe Tzourio,110, 111
Meike W Vernooij,2
Lenore J Launer,112
Charles DeCarli,113, 114
Sudha Seshadri,115, 116
Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium,
Ole A Andreassen,16, 79
Liana G Apostolova,1, 32
Mark E Bastin,30, 42, 43, 117
John Blangero,64
Han G Brunner,5
Randy L Buckner,26, 27, 37, 68
Sven Cichon,75, 76, 118
Giovanni Coppola,32, 119
Greig I de Zubicaray,86
Ian J Deary,30, 31
Gary Donohoe,46, 47
Eco J C de Geus,29
Thomas Espeseth,84, 85, 120
Guill?n Fern?ndez,7, 52, 71
David C Glahn,8, 9
Hans J Grabe,13, 121
John Hardy,54
Hilleke E Hulshoff Pol,15
Mark Jenkinson,122
Ren? S Kahn,15
Colm McDonald,20
Andrew M McIntosh,48
Francis J McMahon,35
Katie L McMahon,123
Andreas Meyer-Lindenberg,25
Derek W Morris,46, 47
Bertram M?ller-Myhsok,49
Thomas E Nichols,122, 124
Roel A Ophoff,15, 65
Tomas Paus,21
Zdenka Pausova,17
Brenda W Penninx,59, 60, 62, 125
Steven G Potkin,51
Philipp G S?mann,49
Andrew J Saykin,33, 34, 95
Gunter Schumann,39
Jordan W Smoller,36, 37
Joanna M Wardlaw,30, 42, 43
Michael E Weale,50
Nicholas G Martin,2, 128
Barbara Franke,5, 6, 7, 128
Margaret J Wright2, 128
& Paul M Thompson1, 128
for the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium129
et al.
AffiliationsContributionsCorresponding author Journal name:
Nature Genetics
Year published:
(2012)
DOI:
doi:10.1038/ng.2250
Received06 September 2011 Accepted19 March 2012 Published online15 April 2012 Article toolsPrint
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ConnoteaCite U LikeFacebookTwitterDeliciousDiggIdentifying 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 disease1, 2 and is reduced in schizophrenia3, major depression4 and mesial temporal lobe epilepsy5. Whereas many brain imaging phenotypes are highly heritable6, 7, 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)
http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2250.html#/supplementary-information
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