Ongoing Natural Selection Shapes Disease-Linked Variants in Living Humans
A study analyzing allele-frequency shifts across age groups in 72,635 Han Taiwanese from the Taiwan Biobank identifies 168 variants showing non-neutral evolution, with 159 under purifying selection and about 90% of these being extremely rare; 71 variants are pathogenic or likely pathogenic, spanning inherited disorders and cancers. The research highlights an unexpected BRCA1 haplotype under purifying selection despite nearby regions in BRCA1/BRCA2/MLH1 showing positive selection, and finds pleiotropic signals in ATG9A and FADS2 affecting lipid metabolism, bone density, and more. Additionally, roughly 150 variants associate with red blood cell traits, potentially reflecting historical malaria adaptation. The study demonstrates that large biobanks can reveal ongoing natural selection in living populations and may refine precision medicine, especially for non-European cohorts.
