School of Medicine Publications and Presentations
Document Type
Article
Publication Date
10-2016
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 novel loci for intracranial volume and confirmed two known signals. Four of the loci are 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 (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth.
Recommended Citation
Adams, H. H., Hibar, D. P., Chouraki, V., Stein, J. L., Nyquist, P. A., Rentería, M. E., Trompet, S., Arias-Vasquez, A., Seshadri, S., Desrivières, S., Beecham, A. H., Jahanshad, N., Wittfeld, K., Van der Lee, S. J., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B. S., … Thompson, P. M. (2016). Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nature neuroscience, 19(12), 1569–1582. https://doi.org/10.1038/nn.4398
Publication Title
Nat Neurosci.
DOI
10.1038/nn.4398
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
Original published version available at https://doi.org/10.1038/nn.4398