Genetics in Context: Social Factors Modify Polygenic Risk Across Multiple Cardiometabolic Diseases

Social vulnerability in the All of Us cohort attenuates polygenic risk score associations with cardiometabolic diseases, including type 2 diabetes, coronary heart disease, and chronic kidney disease.

• Why it matters: PRS-based prediction may not generalize uniformly because genetic–disease links could vary by social determinants of health, a gap that limits equitable risk stratification.
• What they did: Using All of Us, the study tested interactions between PRS and SDoH across eight chronic diseases and built disease-specific polysocial risk scores (PsRS) for joint modeling.
• The result: Joint modeling of PsRS and PRS improved case status prediction across all eight diseases, and PsRS predicted most diseases in external cohorts.

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