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Europeans have a higher proportion of high-frequency deleterious variants than Africans

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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.

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Acknowledgments

The author is grateful to David Lambert and acknowledges the support from Australian Research Council (LP150100583) and Griffith University. We thank Leon Huynen for critical comments. We thank Fernando Racimo for providing the selection coefficient values corresponding to the C scores.

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  1. Environmental Futures Research Institute, Griffith University, 170 Kessels Road, Nathan, QLD, 4111, Australia

    Sankar Subramanian

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  1. Sankar Subramanian
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Correspondence to Sankar Subramanian.

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Subramanian, S. Europeans have a higher proportion of high-frequency deleterious variants than Africans. Hum Genet 135, 1–7 (2016). https://doi.org/10.1007/s00439-015-1604-z

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