No prospective association of a polygenic risk score for coronary artery disease with venous thromboembolism incidence

Background: Previous studies are inconsistent about whether chronic coronary artery disease or generalized atherosclerosis is a causal risk factor for venous thromboembolism. No study seems to have taken a genomic approach to this question. Objective: To test in a prospective study whether a polygenic risk score for coronary artery disease is associated with risk of venous thromboembolism. Participants/Methods: Within the Atherosclerosis Risk in Communities Study cohort, we computed a previously validated polygenic risk score for coronary artery disease among 9144 White participants at baseline in 1987–1989. We followed the participants through 2015 for incident hospitalized venous thromboembolism events, validated by physician review. We used Cox proportional hazards regression to associate quintiles of the polygenic risk score to venous thromboembolism incidence rates. Results: Over the median of 26 years of follow-up, 476 participants had a venous thromboembolism event. There was no apparent association between the coronary artery disease polygenic risk score and incident venous thromboembolism, with age, sex, body mass index adjusted hazard ratios across quintiles being 1 (reference), 0.87 (0.65, 1.15), 1.08 (0.82, 1.42), 0.96 (0.72, 1.27), and 1.03 (0.78, 1.37). Conclusions: A genetic disposition to coronary artery disease did not confer an increased risk of venous thromboembolism in this prospective study.