Cross-ancestry and sex-stratified genome-wide association analyses of amygdala and subnucleus volumes

Abstract The amygdala is a small but critical multi-nucleus structure for emotion, cognition, and neuropsychiatric disorders. Although genetic associations with amygdala and subnucleus volumes have been investigated in sex-mixed European populations, cross-ancestry and sex-stratified analyses are still lacking. Here we conducted cross-ancestry and sex-stratified genome-wide association analyses for 21 amygdala volumetric traits in 6,923 Chinese and 48,634 European individuals. We identified 191 variant-trait associations (P < 2.38 × 10 −9 ), including 47 new associations (12 new loci) in sex-mixed univariate analyses and seven additional new loci in sex-mixed and sex-stratified multivariate analyses. We identified 12 ancestry-specific and two sex-specific associations. The identified genetic variants include 16 fine-mapped causal variants and regulate amygdala and fetal brain gene expression. They are enriched for brain development and affect mood, cognition, and neuropsychiatric disorders. These results indicate that cross-ancestry and sex-stratified genetic association analyses may provide insight into the genetic architectures of amygdala and subnucleus volumes.