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

TitleNovel genetic loci underlying human intracranial volume identified through genome-wide association.
Publication TypeJournal Article
Year of Publication2016
AuthorsAdams HHH, Hibar DP, Chouraki V, Stein JL, Nyquist PA, Renteria ME, Trompet S, Arias-Vasquez A, Seshadri S, Desrivières S et al.
JournalNat Neurosci
Volume19
Issue12
Pagination1569-1582
Date Published2016 Dec
ISSN1546-1726
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 (ρgenetic = 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 their link to physiological and pathological traits.

DOI10.1038/nn.4398
Alternate JournalNat. Neurosci.
PubMed ID27694991
PubMed Central IDPMC5227112
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
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