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


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)).

SUBMITTER: Stein JL 

PROVIDER: S-EPMC3635491 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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

Stein Jason L JL   Medland Sarah E SE   Vasquez Alejandro Arias AA   Hibar Derrek P DP   Senstad Rudy E RE   Winkler Anderson M AM   Toro Roberto R   Appel Katja K   Bartecek Richard R   Bergmann Ørjan Ø   Bernard Manon M   Brown Andrew A AA   Cannon Dara M DM   Chakravarty M Mallar MM   Christoforou Andrea A   Domin Martin M   Grimm Oliver O   Hollinshead Marisa M   Holmes Avram J AJ   Homuth Georg G   Hottenga Jouke-Jan JJ   Langan Camilla C   Lopez Lorna M LM   Hansell Narelle K NK   Hwang Kristy S KS   Kim Sungeun S   Laje Gonzalo G   Lee Phil H PH   Liu Xinmin X   Loth Eva E   Lourdusamy Anbarasu A   Mattingsdal Morten M   Mohnke Sebastian S   Maniega Susana Muñoz SM   Nho Kwangsik K   Nugent Allison C AC   O'Brien Carol C   Papmeyer Martina M   Pütz Benno B   Ramasamy Adaikalavan A   Rasmussen Jerod J   Rijpkema Mark M   Risacher Shannon L SL   Roddey J Cooper JC   Rose Emma J EJ   Ryten Mina M   Shen Li L   Sprooten Emma E   Strengman Eric E   Teumer Alexander A   Trabzuni Daniah D   Turner Jessica J   van Eijk Kristel K   van Erp Theo G M TG   van Tol Marie-Jose MJ   Wittfeld Katharina K   Wolf Christiane C   Woudstra Saskia S   Aleman Andre A   Alhusaini Saud S   Almasy Laura L   Binder Elisabeth B EB   Brohawn David G DG   Cantor Rita M RM   Carless Melanie A MA   Corvin Aiden A   Czisch Michael M   Curran Joanne E JE   Davies Gail G   de Almeida Marcio A A MA   Delanty Norman N   Depondt Chantal C   Duggirala Ravi R   Dyer Thomas D TD   Erk Susanne S   Fagerness Jesen J   Fox Peter T PT   Freimer Nelson B NB   Gill Michael M   Göring Harald H H HH   Hagler Donald J DJ   Hoehn David D   Holsboer Florian F   Hoogman Martine M   Hosten Norbert N   Jahanshad Neda N   Johnson Matthew P MP   Kasperaviciute Dalia D   Kent Jack W JW   Kochunov Peter P   Lancaster Jack L JL   Lawrie Stephen M SM   Liewald David C DC   Mandl René R   Matarin Mar M   Mattheisen Manuel M   Meisenzahl Eva E   Melle Ingrid I   Moses Eric K EK   Mühleisen Thomas W TW   Nauck Matthias M   Nöthen Markus M MM   Olvera Rene L RL   Pandolfo Massimo M   Pike G Bruce GB   Puls Ralf R   Reinvang Ivar I   Rentería Miguel E ME   Rietschel Marcella M   Roffman Joshua L JL   Royle Natalie A NA   Rujescu Dan D   Savitz Jonathan J   Schnack Hugo G HG   Schnell Knut K   Seiferth Nina N   Smith Colin C   Steen Vidar M VM   Valdés Hernández Maria C MC   Van den Heuvel Martijn M   van der Wee Nic J NJ   Van Haren Neeltje E M NE   Veltman Joris A JA   Völzke Henry H   Walker Robert R   Westlye Lars T LT   Whelan Christopher D CD   Agartz Ingrid I   Boomsma Dorret I DI   Cavalleri Gianpiero L GL   Dale Anders M AM   Djurovic Srdjan S   Drevets Wayne C WC   Hagoort Peter P   Hall Jeremy J   Heinz Andreas A   Jack Clifford R CR   Foroud Tatiana M TM   Le Hellard Stephanie S   Macciardi Fabio F   Montgomery Grant W GW   Poline Jean Baptiste JB   Porteous David J DJ   Sisodiya Sanjay M SM   Starr John M JM   Sussmann Jessika J   Toga Arthur W AW   Veltman Dick J DJ   Walter Henrik H   Weiner Michael W MW   Bis Joshua C JC   Ikram M Arfan MA   Smith Albert V AV   Gudnason Vilmundur V   Tzourio Christophe C   Vernooij Meike W MW   Launer Lenore J LJ   DeCarli Charles C   Seshadri Sudha S   Andreassen Ole A OA   Apostolova Liana G LG   Bastin Mark E ME   Blangero John J   Brunner Han G HG   Buckner Randy L RL   Cichon Sven S   Coppola Giovanni G   de Zubicaray Greig I GI   Deary Ian J IJ   Donohoe Gary G   de Geus Eco J C EJ   Espeseth Thomas T   Fernández Guillén G   Glahn David C DC   Grabe Hans J HJ   Hardy John J   Hulshoff Pol Hilleke E HE   Jenkinson Mark M   Kahn René S RS   McDonald Colm C   McIntosh Andrew M AM   McMahon Francis J FJ   McMahon Katie L KL   Meyer-Lindenberg Andreas A   Morris Derek W DW   Müller-Myhsok Bertram B   Nichols Thomas E TE   Ophoff Roel A RA   Paus Tomas T   Pausova Zdenka Z   Penninx Brenda W BW   Potkin Steven G SG   Sämann Philipp G PG   Saykin Andrew J AJ   Schumann Gunter G   Smoller Jordan W JW   Wardlaw Joanna M JM   Weale Michael E ME   Martin Nicholas G NG   Franke Barbara B   Wright Margaret J MJ   Thompson Paul M PM  

Nature genetics 20120415 5


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  ...[more]

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