Biological pathways were evaluated using the Enrichr software33 (http://amp.pharm.mssm.edu/Enrichr/), which considers gene sets derived from population-specific GWAS results and canonical pathways culled from multiple sources (e.g., membership of genes in pathway databases34, protein-protein interaction network data extracted from literature, disease databases35,36, gene expression profiling24,37. Variants were mapped to genes using SNPEff38 and the smallest p -value within each gene was corrected by the effective number of SNPs tested in that gene according to the Li and Ji method39. We set the corrected significance threshold at p < 0.001 in order to obtain 200–300 genes for subsequent pathway analyses. This yielded a list of 235 genes from AAs and EAs. Enrichr uses Fisher’s exact test to calculate an enrichment score. The test for each pathway was computed by comparing its observed rank with the expected rank using multiple random input gene lists.
