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

Rebecca Shafee (), Dustin Moraczewski, Siyuan Liu, Travis Mallard, Adam Thomas and Armin Raznahan ()
Additional contact information
Rebecca Shafee: NIH
Dustin Moraczewski: NIH
Siyuan Liu: NIH
Travis Mallard: Massachusetts General Hospital
Adam Thomas: NIH
Armin Raznahan: NIH

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract Large biobanks have dramatically advanced our understanding of genetic influences on human brain anatomy. However, most studies have combined rather than compared male and female participants. Here we screen for sex differences in the common genetic architecture of over 1000 neuroanatomical phenotypes in the UK Biobank and establish a general concordance between male and female participants in heritability estimates, genetic correlations, and variant-level effects. Notable exceptions include higher mean heritability in the female group for regional volume and surface area phenotypes; between-sex genetic correlations that are significantly below 1 in the insula and parietal cortex; and a common variant with stronger effect in male participants mapping to RBFOX1 - a gene linked to multiple neuropsychiatric disorders more common in men. 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 in growing datasets.

Date: 2024
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DOI: 10.1038/s41467-024-52244-2

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