Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations
- PMID: 30104762
- PMCID: PMC6128408
- DOI: 10.1038/s41588-018-0183-z
Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations
Abstract
A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation1. Proposed clinical applications have largely focused on finding carriers of rare monogenic mutations at several-fold increased risk. Although most disease risk is polygenic in nature2-5, it has not yet been possible to use polygenic predictors to identify individuals at risk comparable to monogenic mutations. Here, we develop and validate genome-wide polygenic scores for five common diseases. The approach identifies 8.0, 6.1, 3.5, 3.2, and 1.5% of the population at greater than threefold increased risk for coronary artery disease, atrial fibrillation, type 2 diabetes, inflammatory bowel disease, and breast cancer, respectively. For coronary artery disease, this prevalence is 20-fold higher than the carrier frequency of rare monogenic mutations conferring comparable risk6. We propose that it is time to contemplate the inclusion of polygenic risk prediction in clinical care, and discuss relevant issues.
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Comment in
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Genetic risks and clinical rewards.Nat Genet. 2018 Sep;50(9):1210-1211. doi: 10.1038/s41588-018-0213-x. Nat Genet. 2018. PMID: 30158681 Free PMC article. No abstract available.
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Bringing polygenic risk scores to the clinic.Nat Med. 2018 Sep;24(9):1303. doi: 10.1038/s41591-018-0190-8. Nat Med. 2018. PMID: 30194405 No abstract available.
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Genome-wide polygenic risk predictors for kidney disease.Nat Rev Nephrol. 2018 Dec;14(12):723-724. doi: 10.1038/s41581-018-0067-6. Nat Rev Nephrol. 2018. PMID: 30279535 Free PMC article.
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The illusion of polygenic disease risk prediction.Genet Med. 2019 Aug;21(8):1705-1707. doi: 10.1038/s41436-018-0418-5. Epub 2019 Jan 12. Genet Med. 2019. PMID: 30635622
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Polygenic Risk Scores That Predict Common Diseases Using Millions of Single Nucleotide Polymorphisms: Is More, Better?Clin Chem. 2019 May;65(5):609-611. doi: 10.1373/clinchem.2018.296103. Epub 2019 Feb 26. Clin Chem. 2019. PMID: 30808642 No abstract available.
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