title: Europeans have a higher proportion of high‑frequency deleterious  variants than Africans.
abstract: Recent studies have shown that a high proportion of rare variants in European and African populations are deleterious in nature. However, the deleterious fraction of high-frequency variants is unclear. Using more than 6500 exomes we show a much higher fraction (11 %) of relatively high-frequency nonsynonymous (amino acid altering) variants (DAF 0.1–10 %) in European Americans (EA) compared to those from African Americans (AA). In contrast, this difference was only marginal (<2 %) for low-frequency nonsynonymous variants (DAF <0.1 %). Our results also revealed that the proportion of high-frequency deleterious nonsynonymous variants in EA was much higher (24 %) than that in AA and this difference was very small (4 %) for the low-frequency deleterious amino acid altering variants. We also show that EA have significantly more number of high-frequency deleterious nonsynonymous variants per genome than AA. The high proportion of high-frequency deleterious variants in EA could be the result of the well-known bottleneck experienced by European populations in which harmful mutations may have drifted to high frequencies. The estimated ages of deleterious variants support this prediction. Our results suggest that high-frequency variants could be relatively more likely to be associated with diseases in Europeans than in Africans and hence emphasize the need for population-specific strategies in genomic medicine studies.
authors.affiliation: Environmental Futures Research Institute, Griffith University, 170 Kessels Road, Nathan, QLD 4111, Australia. s.subramanian@griffith.edu.au
authors.forename: Sankar
authors.initials: S
authors.lastname: Subramanian
mesh_terms: D044383:Black People / Q000235:genetics*; D059472:Exome; D006801:Humans; D009154:Mutation; D044465:White People / Q000235:genetics*; D001741:Black or African American