Identification of common variants associated with human hippocampal and intracranial volumes

Nature Genetics
 
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 Řrjan 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 Muńoz Maniega,30, 42, 43 Kwangsik Nho,33, 44 Allison C Nugent,45 Carol O'Brien,46, 47 Martina Papmeyer,48 Benno Pütz,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 Göring,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 René Mandl,15 Mar Matarin,73 Manuel Mattheisen,75, 76, 77 Eva Meisenzahl,78 Ingrid Melle,16, 79 Eric K Moses,64 Thomas W Mühleisen,75, 76 Matthias Nauck,80 Markus M Nöthen,75, 76, 81 Rene L Olvera,82 Massimo Pandolfo,67 G Bruce Pike,83 Ralf Puls,24 Ivar Reinvang,84, 85 Miguel E Rentería,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 Valdés Hernández,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 Völzke,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 Guillén Fernández,7, 52, 71 David C Glahn,8, 9 Hans J Grabe,13, 121 John Hardy,54 Hilleke E Hulshoff Pol,15 Mark Jenkinson,122 René 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 Müller-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 Sämann,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 Email pdf options download pdf view interactive pdfpowered by ReadCubeDownload citation Order reprints Rights and permissions Share/bookmark 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)
 
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