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bioRxiv · 10.1101/218388

Genome-wide polygenic score to identify a monogenic risk-equivalent for coronary disease

Khera, A. V.·Chaffin, M.·Aragam, K.·Emdin, C. A.·Klarin, D.·Haas, M.·Roselli, C.·Natarajan, P.·Kathiresan, S.
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Abstract

Identification of individuals at increased genetic risk for a complex disorder such as coronary disease can facilitate treatments or enhanced screening strategies. A rare monogenic mutation associated with increased cholesterol is present in ~1:250 carriers and confers an up to 4-fold increase in coronary risk when compared with non-carriers. Although individual common polymorphisms have modest predictive capacity, their cumulative impact can be aggregated into a polygenic score. Here, we develop a new, genome-wide polygenic score that aggregates information from 6.6 million common polymorphisms and show that this score can similarly identify individuals with a 4-fold increased risk for coronary disease. In >400,000 participants from UK Biobank, the score conforms to a normal distribution and those in the top 2.5% of the distribution are at 4-fold increased risk compared to the remaining 97.5%. Similar patterns are observed with genome-wide polygenic scores for two additional diseases - breast cancer and severe obesity.\n\nOne Sentence SummaryA genome-wide polygenic score identifies 2.5% of the population born with a 4-fold increased risk for coronary artery disease.

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Khera, A. V., Chaffin, M., Aragam, K., Emdin, C. A., Klarin, D., Haas, M., Roselli, C., Natarajan, P., Kathiresan, S.. 2017-11-15. Genome-wide polygenic score to identify a monogenic risk-equivalent for coronary disease. https://doi.org/10.1101/218388

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