We also examined the effect of the inferred long-term isolation on genetic drift and natural selection in the Kalash. Our PBS analysis showed evidence of possible positive selection on 1,709 SNPs, of which 762 lie within 548 genes, including RYR2 (MIM: 180902) and ACTN3 (MIM: 102574) (Table S5). IPA showed an enrichment of selection signals in 28 genes associated with cardiovascular physiology and disease pathways (Fisher’s exact test p value = 4.61 × 10−9).