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.

Original publication

DOI

10.1038/nn.4398

Type

Journal article

Journal

Nature neuroscience

Publication Date

12/2016

Volume

19

Pages

1569 - 1582

Addresses

Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.

Keywords

Brain, Humans, Parkinson Disease, Genetic Predisposition to Disease, Cognition, Phenotype, Polymorphism, Single Nucleotide, European Continental Ancestry Group, Oncogene Protein v-akt, Genome-Wide Association Study, Genetic Loci, Phosphatidylinositol 3-Kinases