Identification of common variants associated with human hippocampal and intracranial volumes

the Alzheimer's Disease Neuroimaging Initiative (ADNI), Jason L Stein, Sarah E Medland, Alejandro Arias Vasquez, Derrek P Hibar, Rudy E Senstad, Anderson M Winkler, Roberto Toro, Katja Appel, Richard Bartecek, Orjan Bergmann, Manon Bernard, Andrew A Brown, Dara M Cannon, M Mallar Chakravarty, Andrea Christoforou, Martin Domin, Oliver Grimm, Marisa Hollinshead, Avram J HolmesGeorg Homuth, Jouke-Jan Hottenga, Camilla Langan, Lorna M Lopez, Narelle K Hansell, Kristy S Hwang, Sungeun Kim, Gonzalo Laje, Phil H Lee, Xinmin Liu, Eva Loth, Anbarasu Lourdusamy, Morten Mattingsdal, Sebastian Mohnke, Susana Muñoz Maniega, Kwangsik Nho, Allison C Nugent, Gail Davies, Stephen M Lawrie, David C Liewald, Natalie A Royle, Colin Smith, Maria C Valdés Hernández, Jeremy Hall, David J Porteous, John M Starr, Jessika Sussmann, Mark E Bastin, Ian J Deary, Andrew M McIntosh, Joanna M Wardlaw

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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)).
Original languageEnglish
Pages (from-to)552-561
Number of pages10
JournalNature Genetics
Issue number5
Early online date15 Apr 2012
Publication statusPublished - 2012


Dive into the research topics of 'Identification of common variants associated with human hippocampal and intracranial volumes'. Together they form a unique fingerprint.

Cite this