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Identification of common variants associated with human hippocampal and intracranial volumes

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Authors
Stein, J.
Medland, S.
Vasquez, A.
Hibar, D.
Senstad, R.
Winkler, A.
Toro, R.
Appel, K.
Bartecek, R.
Bergmann, O.
Bernard, M.
Brown, A.
Cannon, D.
Chakravarty, M.
Christoforou, A.
Domin, M.
Grimm, O.
Hollinshead, M.
Holmes, A.
Homuth, G.
Hottenga, J.
Langan, C.
Lopez, L.
Hansell, N.
Hwang, K.
Kim, S.
Laje, G.
Lee, P.
Liu, X.
Loth, E.
Lourdusamy, A.
Mattingsdal, M.
Mohnke, S.
Maniega, S.
Nho, K.
Nugent, A.
O'Brien, C.
Papmeyer, M.
Putz, B.
Ramasamy, A.
Rasmussen, J.
Rijpkema, M.
Risacher, S.
Roddey, J.
Rose, E.
Ryten, M.
Shen, L.
Sprooten, E.
Strengman, E.
Teumer, A.
Trabzuni, D.
Turner, J.
van Eijk, K.
van Erp, T.
van Tol, M.
Wittfeld, K.
Wolf, C.
Woudstra, S.
Aleman, A.
Alhusaini, S.
Almasy, L.
Binder, E.
Brohawn, D.
Cantor, R.
Carless, M.
Corvin, A.
Czisch, M.
Curran, J.
Davies, G.
de Almeida, M.
Delanty, N.
Depondt, C.
Duggirala, R.
Dyer, T.
Erk, S.
Fagerness, J.
Fox, P.
Freimer, N.
Gill, M.
Goering, H.
Hagler, D.
Hoehn, D.
Holsboer, F.
Hoogman, M.
Hosten, N.
Jahanshad, N.
Johnson, M.
Kasperaviciute, D.
Kent, J.
Kochunov, P.
Lancaster, J.
Lawrie, S.
Liewald, D.
Mandl, R.
Matarin, M.
Mattheisen, M.
Meisenzahl, E.
Melle, I.
Moses, Eric
Muehleisen, T.
Nauck, M.
Noethen, M.
Olvera, R.
Pandolfo, M.
Pike, G.
Puls, R.
Reinvang, I.
Renteria, M.
Rietschel, M.
Roffman, J.
Royle, N.
Rujescu, D.
Savitz, J.
Schnack, H.
Schnell, K.
Seiferth, N.
Smith, C.
Steen, V.
Hernandez, M.
Van den Heuvel, M.
van der Wee, N.
Van Haren, N.
Veltman, J.
Voelzke, H.
Walker, R.
Westlye, L.
Whelan, C.
Agartz, I.
Boomsma, D.
Cavalleri, G.
Dale, A.
Djurovic, S.
Drevets, W.
Hagoort, P.
Hall, J.
Heinz, A.
Jack, C.
Foroud, T.
Le Hellard, S.
Macciardi, F.
Montgomery, G.
Poline, J.
Porteous, D.
Sisodiya, S.
Starr, J.
Sussmann, J.
Toga, A.
Veltman, D.
Walter, H.
Weiner, M.
Bis, J.
Ikram, M.
Smith, A.
Gudnason, V.
Tzourio, C.
Vernooij, M.
Launer, L.
DeCarli, C.
Seshadri, S.
Andreassen, O.
Apostolova, L.
Bastin, M.
Blangero, J.
Brunner, H.
Buckner, R.
Cichon, S.
Coppola, G.
de Zubicaray, G.
Deary, I.
Donohoe, G.
de Geus, E.
Espeseth, T.
Fernandez, G.
Glahn, D.
Grabe, H.
Hardy, J.
Pol, H.
Jenkinson, M.
Kahn, R.
McDonald, C.
McIntosh, A.
McMahon, F.
McMahon, K.
Meyer-Lindenberg, A.
Morris, D.
Mueller-Myhsok, B.
Nichols, T.
Ophoff, R.
Paus, T.
Pausova, Z.
Penninx, B.
Potkin, S.
Saemann, P.
Saykin, A.
Schumann, G.
Smoller, J.
Wardlaw, J.
Weale, M.
Martin, N.
Franke, B.
Wright, M.
Thompson, P.
Date
2012
Type
Journal Article

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Citation
Stein, J. and Medland, S. and Vasquez, A. and Hibar, D. and Senstad, R. and Winkler, A. and Toro, R. et al. 2012. Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics. 44 (5): pp. 552-561.
Source Title
Nature Genetics
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School of Pharmacy and Biomedical Sciences
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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). © 2012 Nature America, Inc. All rights reserved.