Clinical use of current polygenic risk scores may exacerbate health disparities

Abstract

Polygenic risk scores (PRS) are poised to improve biomedical outcomes via precision medicine. However, the major ethical and scientific challenge surrounding clinical implementation of PRS is that those available today are several times more accurate in individuals of European ancestry than other ancestries. This disparity is an inescapable consequence of Eurocentric biases in genome-wide association studies, thus highlighting that—unlike clinical biomarkers and prescription drugs, which may individually work better in some populations but do not ubiquitously perform far better in European populations—clinical uses of PRS today would systematically afford greater improvement for European-descent populations. Early diversifying efforts show promise in leveling this vast imbalance, even when non-European sample sizes are considerably smaller than the largest studies to date. To realize the full and equitable potential of PRS, greater diversity must be prioritized in genetic studies, and summary statistics must be publically disseminated to ensure that health disparities are not increased for those individuals already most underserved.

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Fig. 1: Ancestry of GWAS participants over time, as compared with the global population.
Fig. 2: Demographic relationships, allele frequency differences and local LD patterns between population pairs.
Fig. 3: Prediction accuracy relative to European-ancestry individuals across 17 quantitative traits and 5 continental populations in the UKBB.
Fig. 4: Polygenic risk prediction accuracy in Japanese, British and African-descent individuals, on the basis of using independent GWAS of equal sample sizes in the BBJ and UKBB.

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Acknowledgements

We thank A. Khera for helpful discussions. We also thank M. Kubo, Y. Murakami, M. Akiyama and K. Ishigaki for their support in the BBJ Project analysis. We are grateful to S. Gazal for help in calculating LD scores. This work was supported by funding from the National Institutes of Health (K99MH117229 to A.R.M.). UKBB analyses were conducted via application 31063. The BBJ Project was supported by the Tailor-Made Medical Treatment Program of the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) and the Japan Agency for Medical Research and Development (AMED). M.K. was supported by a Nakajima Foundation Fellowship and the Masason Foundation.

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A.R.M. and M.J.D. conceived and designed the experiments. A.R.M. and M.K. performed statistical analysis. A.R.M. and M.K. analyzed the data. A.R.M., M.K., Y.K., Y.O., B.M.N. and M.J.D. contributed reagents/materials/analysis tools. A.R.M., M.K., B.M.N. and M.J.D. wrote the paper.

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Correspondence to Alicia R. Martin.

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Martin, A.R., Kanai, M., Kamatani, Y. et al. Clinical use of current polygenic risk scores may exacerbate health disparities. Nat Genet 51, 584–591 (2019). https://doi.org/10.1038/s41588-019-0379-x

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