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Identification of common variants associated with human hippocampal and intracranial volumes.

Authors: Agartz I, Aleman A, Alhusaini S, Almasy L, Andreassen OA, Apostolova LG, Appel K, Bartecek R, Bastin ME, Bergmann Ø, Bernard M, Binder EB, Bis JC, Blangero J, Boomsma DI, Brohawn DG, Brown AA, Brunner HG, Buckner RL, Cannon DM, Cantor RM, Carless MA, Cavalleri GL, Chakravarty MM, Christoforou A, Cichon S, Coppola G, Corvin A, Curran JE, Czisch M, Dale AM, Davies G, de Almeida MA, de Geus EJ, de Zubicaray GI, Deary IJ, DeCarli C, Delanty N, Depondt C, Djurovic S, Domin M, Donohoe G, Drevets WC, Duggirala R, Dyer TD, Erk S, Espeseth T, Fagerness J, Fernández G, Foroud TM, Fox PT, Franke B, Freimer NB, Gill M, Glahn DC, Göring HH, Grabe HJ, Grimm O, Gudnason V, Hagler DJ, Hagoort P, Hall J, Hansell NK, Hardy J, Heinz A, Hibar DP, Hoehn D, Hollinshead M, Holmes AJ, Holsboer F, Homuth G, Hoogman M, Hosten N, Hottenga JJ, Hulshoff Pol HE, Hwang KS, Ikram MA, Jack CR Jr, Jahanshad N, Jenkinson M, Johnson MP, Kahn RS, Kasperaviciute D, Kent JW Jr, Kim S, Kochunov P, Laje G, Lancaster JL, Langan C, Launer LJ, Lawrie SM, Le Hellard S, Lee PH, Liewald DC, Liu X, Lopez LM, Loth E, Lourdusamy A, Macciardi F, Mandl R, Maniega SM, Martin NG, Matarin M, Mattheisen M, Mattingsdal M, McDonald C, McIntosh AM, McMahon FJ, McMahon KL, Medland SE, Meisenzahl E, Melle I, Meyer-Lindenberg A, Mohnke S, Montgomery GW, Morris DW, Moses EK, Mühleisen TW, Müller-Myhsok B, Nauck M, Nho K, Nichols TE, Nöthen MM, Nugent AC, O'Brien C, Olvera RL, Ophoff RA, Pandolfo M, Papmeyer M, Paus T, Pausova Z, Penninx BW, Pike GB, Poline JB, Porteous DJ, Potkin SG, Puls R, Pütz B, Ramasamy A, Rasmussen J, Reinvang I, Rentería ME, Rietschel M, Rijpkema M, Risacher SL, Roddey JC, Roffman JL, Rose EJ, Royle NA, Rujescu D, Ryten M, Sämann PG, Savitz J, Saykin AJ, Schnack HG, Schnell K, Schumann G, Seiferth N, Senstad RE, Seshadri S, Shen L, Sisodiya SM, Smith AV, Smith C, Smoller JW, Sprooten E, Starr JM, Steen VM, Stein JL, Strengman E, Sussmann J, Teumer A, Thompson PM, Toga AW, Toro R, Trabzuni D, Turner J, Tzourio C, Valdés Hernández MC, Van den Heuvel M, van der Wee NJ, van Eijk K, van Erp TG, Van Haren NE, van Tol MJ, Vasquez AA, Veltman DJ, Veltman JA, Vernooij MW, Völzke H, Walker R, Walter H, Wardlaw JM, Weale ME, Weiner MW, Westlye LT, Whelan CD, Winkler AM, Wittfeld K, Wolf C, Woudstra S, Wright MJ

Journal: Nature Genetics

Volume & Issue: 44 & 5

Page No.: 552-61

DOI: 10.1038/ng.2250

Year Published: 2012

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)).