Models combining clinical history with polygenic scores were developed and validated for 150 diseases and all-cause mortality in 900,000 UK Biobank and FinnGen participants. Genetic information added most in metabolic, cardiovascular, autoimmune and neurological disease, with larger gains at lower clinical risk. For atherosclerotic cardiovascular disease, the score expanded the high-risk group by 40%, and those reclassified had 4.9 times the incidence of those remaining low-risk.
Why it is interesting: Genetic scores add least where clinical records already identify risk, and most where they do not.
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