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Journal Article

Identification of common variants associated with human hippocampal and intracranial volumes

MPS-Authors
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Hoogman,  Martine
Donders Institute for Brain, Cognition and Behaviour, External Organizations;
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;

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Hagoort,  Peter
Neurobiology of Language Department, MPI for Psycholinguistics, Max Planck Society;
Donders Institute for Brain, Cognition and Behaviour, External Organizations;

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Fulltext (public)

Stein_et_al_Nature_Genetics_2012.pdf
(Publisher version), 1023KB

Supplementary Material (public)

Stein_Nature_Genetics_2012_Suppl_Info.pdf
(Supplementary material), 26MB

Citation

Stein, J. L., Medland, S. E., Vasquez, A. A., Hibar, D. P., Senstad, R. E., Winkler, A. M., et al. (2012). Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics, 44, 552-561. doi:10.1038/ng.2250.


Cite as: https://hdl.handle.net/11858/00-001M-0000-000F-471E-E
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)).