Authors: Stein JL; Medland SE; Vasquez AA; Hibar DP; Senstad RE; Winkler AM; Toro R; Appel K; Bartecek R; Bergmann Ã; Bernard M; Brown AA; Cannon DM; Chakravarty MM; Christoforou A; Domin M; Grimm O; Hollinshead M; Holmes AJ; Homuth G; Hottenga JJ; Langan C; Lopez LM; Hansell NK; Hwang KS; Kim S; Laje G; Lee PH; Liu X; Loth E; Lourdusamy A; Mattingsdal M; Mohnke S; Maniega SM; Nho K; Nugent AC; O'Brien C; Papmeyer M; Pütz B; Ramasamy A; Rasmussen J; Rijpkema M; Risacher SL; Roddey JC; Rose EJ; Ryten M; Shen L; Sprooten E; Strengman E; Teumer A; Trabzuni D; Turner J; van Eijk K; van Erp TG; van Tol MJ; Wittfeld K; Wolf C; Woudstra S; Aleman A; Alhusaini S; Almasy L; Binder EB; Brohawn DG; Cantor RM; Carless MA; Corvin A; Czisch M; Curran JE; Davies G; de Almeida MA; Delanty N; Depondt C; Duggirala R; Dyer TD; Erk S; Fagerness J; Fox PT; Freimer NB; Gill M; Göring HH; Hagler DJ; Hoehn D; Holsboer F; Hoogman M; Hosten N; Jahanshad N; Johnson MP; Kasperaviciute D; Kent JW Jr; Kochunov P; Lancaster JL; Lawrie SM; Liewald DC; Mandl R; Matarin M; Mattheisen M; Meisenzahl E; Melle I; Moses EK; Mühleisen TW; Nauck M; Nöthen MM; Olvera RL; Pandolfo M; Pike GB; Puls R; Reinvang I; RenterÃa ME; Rietschel M; Roffman JL; Royle NA; Rujescu D; Savitz J; Schnack HG; Schnell K; Seiferth N; Smith C; Steen VM; Valdés Hernández MC; Van den Heuvel M; van der Wee NJ; Van Haren NE; Veltman JA; Völzke H; Walker R; Westlye LT; Whelan CD; Agartz I; Boomsma DI; Cavalleri GL; Dale AM; Djurovic S; Drevets WC; Hagoort P; Hall J; Heinz A; Jack CR Jr; Foroud TM; Le Hellard S; Macciardi F; Montgomery GW; Poline JB; Porteous DJ; Sisodiya SM; Starr JM; Sussmann J; Toga AW; Veltman DJ; Walter H; Weiner MW; Alzheimer's Disease Neuroimaging Initiative; EPIGEN Consortium; IMAGEN Consortium; Saguenay Youth Study Group; Bis JC; Ikram MA; Smith AV; Gudnason V; Tzourio C; Vernooij MW; Launer LJ; DeCarli C; Seshadri S; Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium; Andreassen OA; Apostolova LG; Bastin ME; Blangero J; Brunner HG; Buckner RL; Cichon S; Coppola G; de Zubicaray GI; Deary IJ; Donohoe G; de Geus EJ; Espeseth T; Fernández G; Glahn DC; Grabe HJ; Hardy J; Hulshoff Pol HE; Jenkinson M; Kahn RS; McDonald C; McIntosh AM; McMahon FJ; McMahon KL; Meyer-Lindenberg A; Morris DW; Müller-Myhsok B; Nichols TE; Ophoff RA; Paus T; Pausova Z; Penninx BW; Potkin SG; Sämann PG; Saykin AJ; Schumann G; Smoller JW; Wardlaw JM; Weale ME; Martin NG; Franke B; Wright MJ; Thompson PM; Enhancing Neuro Imaging Genetics through Meta-Analysis Consortium
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 x 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 x 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 x 10(-7)).
Keywords: Brain/*physiopathology; Chromosomes, Human, Pair 12/*genetics; Genetic Loci; Genetic Markers; Genome-Wide Association Study; Hippocampus/*physiopathology; Humans; Meta-Analysis as Topic; *Neuroimaging; Polymorphism, Single Nucleotide/*genetics|
Journal: Nature genetics Volume: 44 Issue: 5 Pages: 552-61 Date: April 17, 2012 PMID: 22504417 |
Stein JL, Medland SE, Vasquez AA, Hibar DP, Senstad RE, Winkler AM, Toro R, Appel K, Bartecek R, Bergmann Ã, Bernard M, Brown AA, Cannon DM, Chakravarty MM, Christoforou A, Domin M, Grimm O, Hollinshead M, Holmes AJ, Homuth G, Hottenga JJ, Langan C, Lopez LM, Hansell NK, Hwang KS, Kim S, Laje G, Lee PH, Liu X, Loth E, Lourdusamy A, Mattingsdal M, Mohnke S, Maniega SM, Nho K, Nugent AC, O'Brien C, Papmeyer M, Pütz B, Ramasamy A, Rasmussen J, Rijpkema M, Risacher SL, Roddey JC, Rose EJ, Ryten M, Shen L, Sprooten E, Strengman E, Teumer A, Trabzuni D, Turner J, van Eijk K, van Erp TG, van Tol MJ, Wittfeld K, Wolf C, Woudstra S, Aleman A, Alhusaini S, Almasy L, Binder EB, Brohawn DG, Cantor RM, Carless MA, Corvin A, Czisch M, Curran JE, Davies G, de Almeida MA, Delanty N, Depondt C, Duggirala R, Dyer TD, Erk S, Fagerness J, Fox PT, Freimer NB, Gill M, Göring HH, Hagler DJ, Hoehn D, Holsboer F, Hoogman M, Hosten N, Jahanshad N, Johnson MP, Kasperaviciute D, Kent JW Jr, Kochunov P, Lancaster JL, Lawrie SM, Liewald DC, Mandl R, Matarin M, Mattheisen M, Meisenzahl E, Melle I, Moses EK, Mühleisen TW, Nauck M, Nöthen MM, Olvera RL, Pandolfo M, Pike GB, Puls R, Reinvang I, RenterÃa ME, Rietschel M, Roffman JL, Royle NA, Rujescu D, Savitz J, Schnack HG, Schnell K, Seiferth N, Smith C, Steen VM, Valdés Hernández MC, Van den Heuvel M, van der Wee NJ, Van Haren NE, Veltman JA, Völzke H, Walker R, Westlye LT, Whelan CD, Agartz I, Boomsma DI, Cavalleri GL, Dale AM, Djurovic S, Drevets WC, Hagoort P, Hall J, Heinz A, Jack CR Jr, Foroud TM, Le Hellard S, Macciardi F, Montgomery GW, Poline JB, Porteous DJ, Sisodiya SM, Starr JM, Sussmann J, Toga AW, Veltman DJ, Walter H, Weiner MW, Alzheimer's Disease Neuroimaging Initiative, EPIGEN Consortium, IMAGEN Consortium, Saguenay Youth Study Group, Bis JC, Ikram MA, Smith AV, Gudnason V, Tzourio C, Vernooij MW, Launer LJ, DeCarli C, Seshadri S, Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, Andreassen OA, Apostolova LG, Bastin ME, Blangero J, Brunner HG, Buckner RL, Cichon S, Coppola G, de Zubicaray GI, Deary IJ, Donohoe G, de Geus EJ, Espeseth T, Fernández G, Glahn DC, Grabe HJ, Hardy J, Hulshoff Pol HE, Jenkinson M, Kahn RS, McDonald C, McIntosh AM, McMahon FJ, McMahon KL, Meyer-Lindenberg A, Morris DW, Müller-Myhsok B, Nichols TE, Ophoff RA, Paus T, Pausova Z, Penninx BW, Potkin SG, Sämann PG, Saykin AJ, Schumann G, Smoller JW, Wardlaw JM, Weale ME, Martin NG, Franke B, Wright MJ, Thompson PM, Enhancing Neuro Imaging Genetics through Meta-Analysis Consortium (2012) Identification of common variants associated with human hippocampal and intracranial volumes. Nature genetics 44: 552-61.
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