Using sex‐specific polygenic risk to prognosticate coronary artery disease in women

Kaavya Paruchuri, Rohan Bhukar, Sarah Urbut, Yunfeng Ruan, Shriienidhie Ganesh, Pradeep Natarajan

Abstract:

Despite advances, cardiovascular disease remains the leading killer in women. Compared with men, the risk is underrecognized and diagnosis is delayed, contributing to overall worse coronary artery disease (CAD) outcomes.1 The mechanisms for elevated risk in women remain incompletely explained by conventional risk factors. The role of varying genetic effects in this elevation remains uncertain. Genome‐wide association studies have enabled the discovery of genetic variants associated with CAD and other complex diseases. A CAD polygenic risk score (PRS) sums individually modest effects from CAD risk alleles and can be used with traditional risk calculators to independently predict and jointly improve CAD risk discrimination.2
Characterizing and understanding generalizability of a novel biomarker is critical to ensure disparities are not exacerbated. Analyses in the UK Biobank indicate older CAD PRS performs worse in women relative to men.1 Whether similar performance differences exist in modern US populations with novel CAD PRS is unknown, and strategies to mitigate this bias are unclear.