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A substantial proportion of the adult US population with type 2 diabetes (T2D) are undiagnosed, calling into question the comprehensiveness of current screening practices, which primarily rely on age, family history, and body mass index (BMI). We hypothesized that a polygenic score (PGS) may serve as a complementary tool to identify high-risk individuals. The T2D PGS maintained predictive utility after adjusting for family history and combining genetics with family history led to even more improved disease risk prediction. We observed that the PGS was meaningfully related to age of onset with implications for screening practices: there was a linear and statistically significant relationship between the PGS and T2D onset (-1.3 years per standard deviation of the PGS). Evaluation of U.S. Preventive Task Force and a simplified version of American Diabetes Association screening guidelines showed that addition of a screening criterion for those above the 90th percentile of the PGS provided

San diegoUnited statesPattillo smithJb meigset alAssociation of polygenic risk scoreUs preventive service taskMe personal genome serviceNational institute of diabetesMe incAmerican diabetes associationNational diabetes statisticsEthical independent review servicesUs preventive services taskCenters for diseaseIus dept of healthRisk state for diabetes development