A sex-stratified analysis of the genetic architecture of human brain anatomy

Large biobanks have dramatically advanced our understanding of genetic influences on human brain anatomy. However, most studies have combined rather than compared males and females - despite theoretical grounds for potential sex differences. By systematically screening for sex differences in the common genetic architecture of > 1000 neuroanatomical phenotypes in the UK Biobank, we establish a general concordance between males and females in heritability estimates, genetic correlations and variant-level effects. Notable exceptions include: higher mean h in females for regional volume and surface area phenotypes; between-sex genetic correlations that are significantly below 1 in the insula and parietal cortex; and, a male-specific effect common variant mapping to RBFOX1 - a gene linked to multiple male-biased neuropsychiatric disorders. This work suggests that common variant influences on human brain anatomy are largely consistent between males and females, with a few exceptions that will guide future research as biobanks continue to grow in size.