We reasoned that ancestry-associated DEGs may contain risk genes that explain susceptibility to brain-related illnesses based on ancestry. To explore this hypothesis, we conducted stratified linkage disequilibrium (LD) score (S-LDSC32) regression to assess the polygenic contributions of global ancestry-associated DEGs to 17 brain-related traits (for example, attention-deficit/hyperactivity disorder (ADHD), autism, body mass index BMI), depression and schizophrenia) and five immune-related traits as a positive control. Overall, we observed enrichment for heritability of neurological disorders and immune-related traits but not for psychiatric disorders and behavioral traits (Fig. 6, Supplementary Fig. 30 and Supplementary Data 10). This also included limited enrichment of peripheral immune function33–35 (Fisher’s exact test, FDR < 0.05; Supplementary Fig. 31), which is consistent with our previous finding of a stronger association with brain immune cell types compared to non-brain immune cell types (Supplementary Fig. 12).
