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

Hieab H H Adams, Derrek P. Hibar, Vincent Chouraki, Jason L. Stein, Paul A. Nyquist, Miguel E. Rentería, Stella Trompet, Alejandro Arias-Vasquez, Sudha Seshadri, Sylvane Desrivières, Ashley H. Beecham, Neda Jahanshad, Katharina Wittfeld, Sven J. Van Der Lee, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S. AribisalaVelandai Srikanth

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117 Citations (Scopus)

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 (N combined = 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.

Original languageEnglish
Pages (from-to)1569-1582
Number of pages14
JournalNature Neuroscience
Volume19
Issue number12
DOIs
Publication statusPublished - 1 Dec 2016

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