The Genetic Architecture of Amygdala Nuclei

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

“…We identified 191 unique variant-trait associations, 136 unique locus-trait associations, and 30 LD-independent loci at P < 2.38 × 10 −9 (Supplementary Tables 7-10). To identify new associations and loci, we integrated all previous univariate GWASs with available summary statistics for amygdala volumetric traits [20][21][22][23][24][25] to define the references (P < 2.38 × 10 −9 ) of known variant-trait associations (n = 200), locus-trait associations (n = 158), and LD-independent loci (n = 37). With the EUR-LD reference and the same threshold (P < 2.38 × 10 −9 ), we defined a novel variant-trait association if the variant was 500 kb away from and not in LD (r 2 < 0.1) with any variants of the same trait in the list of known variant-trait associations; a novel locus-trait association when all lead variants in the locus were 500 kb away from and not in LD (r 2 < 0.1) with any lead variants in the loci of all known locus-trait associations; and a novel locus when all lead variants in the locus were 500 kb away from and not in LD (r 2 < 0.1) with any lead variants in known loci.…”

“…Based on the pooled associations and loci from the sex-mixed univariate GWASs, we identified new variant-trait associations, locus-trait associations, and amygdalaassociated loci by comparing them with those associations/loci identified in previous GWASs for the amygdala volumetric traits (P < 5 × 10 −8 and P < 2.38 × 10 −9 ) [20][21][22][23][24][25] , in which the EUR-LD reference was used since all previous GWASs for traits were conducted in EUR participants. We considered a variant-trait association as new when the variant was 500 kb away from and not in LD (r 2 < 0.1) with any known independent variants associated with the same trait.…”

“…A new C-GWAS locus was confirmed when the lead variant in the locus was 500 kb away from and not in LD (r 2 < 0.1) with loci identified by univariate GWASs at P < 2.38 × 10 −9 . For the new loci, we used the same method to test whether they were reported in previous univariate GWASs [20][21][22][23][24][25] .…”

“…The volumes of the human amygdala and subnuclei can be quantified by the structural magnetic resonance imaging (MRI) technique 19 . As heritable brain imaging phenotypes, several genome-wide association studies (GWASs) have been conducted to investigate the genetic architectures of amygdala and subnucleus volumes in sexmixed individuals of European ancestry (EUR) [20][21][22][23][24][25] . However, the sex-mixed EUR-GWASs cannot answer the question of whether there are ancestry-specific and sexspecific genetic associations with amygdala volumetric traits.…”