Genome-wide polygenic scores quantify inherited risk by integrating information from many common DNA variants and hold considerable promise for enabling personalized medicine. By integrating information on coronary artery disease (CAD) and CAD-related risk traits from genetic datasets that were larger and more diverse than those used in the past, we developed an improved multi-ancestry polygenic predictor for CAD.
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References
Patel, A. P. & Khera, A. V. Advances and applications of polygenic scores for coronary artery disease. Annu. Rev. Med. 74, 141–154 (2023). This review describes the historical underpinnings of polygenic score development, the current state of the field as it relates to CAD, and knowledge and implementation gaps.
Martin, A. R. et al. Current clinical use of polygenic scores will risk exacerbating health disparities. Nat. Genet. 51, 584–591 (2019). This paper calls attention to the decreased performance of polygenic scores in people of non-European ancestries relative to their performance in those of European ancestry.
Aragam, K. G. et al. Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants. Nat. Genet. 54, 1803–1815 (2022). This is an international consortium effort to meta-analyze data from more than 160,000 CAD cases that identified nearly 200 risk loci.
Tcheandjieu, C. et al. Large-scale genome-wide association study of coronary artery disease in genetically diverse populations. Nat. Med. 28, 1679–1692 (2022). This paper reports GWAS data from the Million Veterans Program, including populations of African, European and Hispanic ancestry.
Khera, A. V. et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat. Genet. 50, 1219–1224 (2018). This paper presents genome-wide polygenic scores for five common diseases, identifying people in the tails of the score distribution who have a risk equivalent to that of carriers of a rare monogenic variant.
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This is a summary of: Patel, A. P. et al. A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease. Nat. Med. https://doi.org/10.1038/s41591-023-02429-x (2023).
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Improving polygenic score prediction for coronary artery disease across populations of diverse ancestry. Nat Med 29, 1621–1622 (2023). https://doi.org/10.1038/s41591-023-02451-z
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DOI: https://doi.org/10.1038/s41591-023-02451-z
