313: Integrating Polygenic Risk Scores and Social Determinants of Health across Populations

Cromer SJ et al., The American Journal of Human Genetics - This paper reviews polygenic risk scores (PRS) and social determinants of health (SDoH) and outlines best practices for integrating PRS and SDoH across diverse populations to improve prediction and equity. Key terms: polygenic risk scores, social determinants of health, PRS transferability, data harmonization, type 2 diabetes.

Study Highlights:
This review focuses on human populations and uses conceptual frameworks, hypothetical population examples, and synthesis of methodological studies to evaluate PRS and SDoH integration. It summarizes methods for PRS construction and transferability, SDoH measurement at individual and area levels, and analytic approaches including interaction, mediation, and calibration. Quantitatively, the authors note substantial declines in PRS predictive accuracy when applied to genetically distinct populations (for example, African-ancestry performance often ~20–40% of European-derived PRS). The review highlights harmonization, population-specific calibration, and interdisciplinary teams as functional steps to improve predictive validity and reduce inequitable impacts.

Conclusion:
Integrating PRSs with carefully measured and harmonized SDoH across diverse populations requires population-aware conceptual frameworks, calibrated analytic methods, diverse datasets, and ethical safeguards to improve predictive validity and equity.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Incorporating polygenic risk scores and social determinants of health across populations: Considerations and best practices in research

First author:
Cromer SJ

Journal:
The American Journal of Human Genetics

DOI:
10.1016/j.ajhg.2026.02.007

Reference:
Cromer SJ, Cobran EK, Iyer HS, Hysong MR, Vargas LB, Smith JL, Konigsberg IR, Bogumil D, Glover L, King G, PRIMED Consortium SDoH Working Group, Lange LA, Patel A, Wojcik G, Raffield L, Conti DV, et al. Incorporating polygenic risk scores and social determinants of health across populations: Considerations and best practices in research. The American Journal of Human Genetics. 2026;113:1–25. https://doi.org/10.1016/j.ajhg.2026.02.007

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-03-10.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited substantive sections of the transcript covering PRS basics, PRS transferability across populations, SDoH domains and measurement, harmonization challenges, analytical frameworks (main effects, interactions, mediation), T2D as an illustrative case, and ethical considerations.
- transcript topics: PRS basics and transferability; SDoH four-domain framework (socioeconomic, sociocultural, physical environment, healthcare access); Individual vs area-level SDoH measures; SDoH harmonization across datasets; Analytical frameworks (main effects, interaction/effect modification, mediation); T2D as illustrative example

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 8
- claims flagged for review: 0
- metadata chec...