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Identification of common variants associated with human hippocampal and intracranial volumes

Stein, Jason L, Medland, Sarah E, Vasquez, Alejandro Arias, Hibar, Derrek P, Senstad, Rudy E, Winkler, Anderson M, Toro, Roberto, Appel, Katja, Bartecek, Richard, Bergmann, Ørjan, Bernard, Manon, Brown, Andrew A, Cannon, Dara M, Chakravarty, M Mallar, Christoforou, Andrea, Domin, Martin, Grimm, Oliver, Hollinshead, Marisa, Holmes, Avram J, Homuth, Georg, Hottenga, Jouke-Jan, Langan, Camilla, Lopez, Lorna M, Hansell, Narelle K, Hwang, Kristy S, Kim, Sungeun, Laje, Gonzalo, Lee, Phil H, Liu, Xinmin, Loth, Eva, Lourdusamy, Anbarasu, Mattingsdal, Morten, Mohnke, Sebastian, Maniega, Susana Muñoz, Nho, Kwangsik, Nugent, Allison C, O'Brien, Carol, Papmeyer, Martina, Pütz, Benno, Ramasamy, Adaikalavan, Rasmussen, Jerod, Rijpkema, Mark, Risacher, Shannon L, Roddey, J Cooper, Rose, Emma J, Ryten, Mina, Shen, Li, Sprooten, Emma, Strengman, Eric, Teumer, Alexander, Trabzuni, Daniah, Turner, Jessica, van Eijk, Kristel, van Erp, Theo G M, van Tol, Marie-Jose, Wittfeld, Katharina, Wolf, Christiane, Woudstra, Saskia, Aleman, Andre, Alhusaini, Saud, Almasy, Laura, Binder, Elisabeth B, Brohawn, David G, Cantor, Rita M, Carless, Melanie A, Corvin, Aiden, Czisch, Michael, Curran, Joanne E, Davies, Gail, de Almeida, Marcio A A, Delanty, Norman, Depondt, Chantal, Duggirala, Ravi, Dyer, Thomas D, Erk, Susanne, Fagerness, Jesen, Fox, Peter T, Freimer, Nelson B, Gill, Michael, Göring, Harald H H, Hagler, Donald J, Hoehn, David, Holsboer, Florian, Hoogman, Martine, Hosten, Norbert, Jahanshad, Neda, Johnson, Matthew P, Kasperaviciute, Dalia, Kent, Jack W, Kochunov, Peter, Lancaster, Jack L, Lawrie, Stephen M, Liewald, David C, Mandl, René, Matarin, Mar, Mattheisen, Manuel, Meisenzahl, Eva, Melle, Ingrid, Moses, Eric K, Mühleisen, Thomas W, Nauck, Matthias, Nöthen, Markus M, Olvera, Rene L, Pandolfo, Massimo, Pike, G Bruce, Puls, Ralf, Reinvang, Ivar, Rentería, Miguel E, Rietschel, Marcella, Roffman, Joshua L, Royle, Natalie A, Rujescu, Dan, Savitz, Jonathan, Schnack, Hugo G, Schnell, Knut, Seiferth, Nina, Smith, Colin, Steen, Vidar M, Valdés Hernández, Maria C, Van den Heuvel, Martijn, van der Wee, Nic J, Van Haren, Neeltje E M, Veltman, Joris A, Völzke, Henry, Walker, Robert, Westlye, Lars T, Whelan, Christopher D, Agartz, Ingrid, Boomsma, Dorret I, Cavalleri, Gianpiero L, Dale, Anders M, Djurovic, Srdjan, Drevets, Wayne C, Hagoort, Peter, Hall, Jeremy, Heinz, Andreas, Jack, Clifford R, Foroud, Tatiana M, Le Hellard, Stephanie, Macciardi, Fabio, Montgomery, Grant W, Poline, Jean Baptiste, Porteous, David J, Sisodiya, Sanjay M, Starr, John M, Sussmann, Jessika, Toga, Arthur W, Veltman, Dick J, Walter, Henrik, Weiner, Michael W, Bis, Joshua C, Ikram, M Arfan, Smith, Albert V, Gudnason, Vilmundur, Tzourio, Christophe, Vernooij, Meike W, Launer, Lenore J, DeCarli, Charles, Seshadri, Sudha, Andreassen, Ole A, Apostolova, Liana G, Bastin, Mark E, Blangero, John, Brunner, Han G, Buckner, Randy L, Cichon, Sven, Coppola, Giovanni, de Zubicaray, Greig I, Deary, Ian J, Donohoe, Gary, de Geus, Eco J C, Espeseth, Thomas, Fernández, Guillén, Glahn, David C, Grabe, Hans J, Hardy, John, Hulshoff Pol, Hilleke E, Jenkinson, Mark, Kahn, René S, McDonald, Colm, McIntosh, Andrew M, McMahon, Francis J, McMahon, Katie L, Meyer-Lindenberg, Andreas, Morris, Derek W, Müller-Myhsok, Bertram, Nichols, Thomas E, Ophoff, Roel A, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W, Potkin, Steven G, Sämann, Philipp G, Saykin, Andrew J, Schumann, Gunter, Smoller, Jordan W, Wardlaw, Joanna M, Weale, Michael E, Martin, Nicholas G, Franke, Barbara, Wright, Margaret J and Thompson, Paul M 2012. Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics 44 (5) , pp. 552-561. 10.1038/ng.2250

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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)).

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
Publisher: Nature Publishing Group
ISSN: 1061-4036
Last Modified: 04 Jun 2017 08:32
URI: http://orca.cf.ac.uk/id/eprint/79858

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