Abstract
Introduction Most strategies for prevention of venous thromboembolism focus on preventing recurrent events. Yet, primary prevention might be possible through approaches targeting the whole population or high-risk patients. To inform possible prevention strategies, population-based information on the ability of genetic risk scores to identify risk of incident venous thromboembolism is needed. Materials and methods We used proportional hazards regression to relate two published genetic risk scores (273-variants versus 5-variants) with venous thromboembolism incidence in the Atherosclerosis Risk in Communities Study (ARIC) cohort (n = 11,292), aged 45–64 at baseline, drawn from 4 US communities. Results Over a median of 28 years, ARIC identified 788 incident venous thromboembolism events. Incidence rates rose more than two-fold across quartiles of the 273-variant genetic risk score: 1.7, 2.7, 3.4 and 4.0 per 1,000 person-years. For White participants, age, sex, and ancestry-adjusted hazard ratios (95% confidence intervals) across quartiles were strong [1 (reference), 1.30 (0.99,1.70), 1.85 (1.43,2.40), and 2.58 (2.04,3.28)] but weaker for Black participants [1, 1.05 (0.63,1.75), 1.37 (0.84,2.22), and 1.32 (0.80,2.20)]. The 5-variant genetic risk score showed a less steep gradient, with hazard ratios in Whites of 1, 1.17 (0.89,1.54), 1.48 (1.14,1.92), and 2.18 (1.71,2.79). Models including the 273-variant genetic risk score plus lifestyle and clinical factors had a c-statistic of 0.67. Conclusions In the general population, middle-aged adults in the highest quartile of either genetic risk score studied have approximately two-fold higher risk of an incident venous thromboembolism compared with the lowest quartile. The genetic risk scores show a weaker association with venous thromboembolism for Black people.
| Original language | English (US) |
|---|---|
| Article number | e0280657 |
| Journal | PloS one |
| Volume | 18 |
| Issue number | 1 January |
| DOIs | |
| State | Published - Jan 2023 |
Bibliographical note
Funding Information:Funding: The National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services has funded the Atherosclerosis Risk in Communities study with Federal Contract nos. HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, HHSN268201700005I, and the study of venous thromboembolism with grant R01HL059367 (ARF). NP and JAL were partially funded by R01HL154385. Genomics funding for the Atherosclerosis Risk in Communities Study also came from R01HL087641 and R01HL086694, National Human Genome Research Institute contract U01HG004402, and National Institutes of Health contract HHSN268200625226C. The funders had no role in the study design data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank the staff and participants of the ARIC study for their important contributions.
Publisher Copyright:
Copyright: © 2023 Folsom et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.