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Journal Article

Novel genetic loci underlying human intracranial volume identified through genome-wide association

MPS-Authors
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Guadalupe,  Tulio
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
International Max Planck Research School for Language Sciences, MPI for Psycholinguistics, Max Planck Society, Nijmegen, NL;

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Fisher,  Simon E.
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
Donders Institute for Brain, Cognition and Behaviour, External Organizations;

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Francks,  Clyde
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
Donders Institute for Brain, Cognition and Behaviour, External Organizations;
Imaging Genomics, MPI for Psycholinguistics, Max Planck Society;

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http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.4398.html#supplementary-information
(Supplementary material)

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Adams_etal_2016.pdf
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Citation

Adams, H. H. H., Hibar, D. P., Chouraki, V., Stein, J. L., Nyquist, P., Renteria, M. E., et al. (2016). Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nature Neuroscience, 19, 1569-1582. doi:10.1038/nn.4398.


Cite as: https://hdl.handle.net/11858/00-001M-0000-002B-7F28-6
Abstract
Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late
life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438
adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were
also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height.
We found a high genetic correlation with child head circumference (genetic = 0.748), which indicates a similar genetic
background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial
volume were also related to childhood and adult cognitive function, and Parkinson’s disease, and were enriched near genes
involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial
volume and provide genetic support for theories on brain reserve and brain overgrowth.