Prediction of venous thromboembolism incidence in the general adult population using two published genetic risk scores

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 g...

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Bibliographic Details
Published in:PloS one Vol. 18; no. 1; p. e0280657
Main Authors: Folsom, Aaron R., Tang, Weihong, Hong, Ching-Ping, Rosamond, Wayne D., Lane, John A., Cushman, Mary, Pankratz, Nathan
Format: Journal Article
Language:English
Published: United States Public Library of Science 30.01.2023
Public Library of Science (PLoS)
Subjects:
Adult
Arteriosclerosis
Atherosclerosis
Atherosclerosis - complications
Biology and Life Sciences
Black People
Confidence intervals
Diabetes
Genetic aspects
Genetic markers
Genetic research
Genetic variation
Genomes
Health risks
Hormone replacement therapy
Humans
Incidence
Lifestyles
Medical research
Medicine and Health Sciences
Medicine, Experimental
Middle Aged
Population (statistical)
Population genetics
Prevention
Proportional Hazards Models
Quality control
Quartiles
Risk
Risk Factors
Risk groups
Social Sciences
Statistical analysis
Statistics
Thromboembolism
Venous Thromboembolism - epidemiology
Venous Thromboembolism - genetics
United States
United States > US
ISSN:1932-6203, 1932-6203
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Summary: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. 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. 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. 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.
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Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0280657