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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, et al.
Secondary AuthorsThompson PM
JournalNat Neurosci
Volume19
Issue12
Pagination1569-1582
Date Published2016 12
ISSN1546-1726
KeywordsBrain, Cognition, European Continental Ancestry Group, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Oncogene Protein v-akt, Parkinson Disease, Phenotype, Phosphatidylinositol 3-Kinases, Polymorphism, Single Nucleotide
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 (ρ = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N = 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 ListHHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
RC2 MH089951 / MH / NIMH NIH HHS / United States
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R01 HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
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ZIA MH002810 / ImNIH / Intramural NIH HHS / United States
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MR/L501542/1 / MRC_ / Medical Research Council / United Kingdom
RF1 AG041915 / AG / NIA NIH HHS / United States
K99 MH102357 / MH / NIMH NIH HHS / United States
R01 MH062873 / MH / NIMH NIH HHS / United States
G0802462 / MRC_ / Medical Research Council / United Kingdom
K24 MH094614 / MH / NIMH NIH HHS / United States
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RF1 AG015819 / AG / NIA NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
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104036 / WT_ / Wellcome Trust / United Kingdom
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