Abstract
Introduction: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality. The Factor V Leiden (FVL) variant is a well-described genetic risk factor for VTE. The extent to which FVL exerts influence on VTE risk by age is not well understood. Hypothesis: The VTE risk conferred by the FVL variant is dependent on age. Methods: We utilized a Cox proportional hazards model to calculate the hazard ratio (HR) for incident VTE in individuals in the UK Biobank with one or two alleles of the common FVL variant, rs6025 (chr1:169549811 (GRCh38.p13) C>T) adjusting for age, sex, diabetes mellitus type 2, smoking history, scaled body-mass index, and the first ten principal components. We further examined the relationship of rs6025-related VTE risk with age by performing Cox proportional hazard regression in individuals aged 40-49, 50-59, and 60-69 years. Analyses were conducted in R-4.0. Results: Among 413,722 individuals followed for median of 7 years, 3218 (0.78%) incident VTE events occurred. The presence of the rs6025 variant (allele frequency 0.047) was associated with a 1.7 hazard ratio (HR) of VTE (CI 1.38-2.07, p=2x10 -7 ) overall. However, the relative effects varied by age with hazard ratios for individuals 40-49 years, 50-59 years, and 60-69 years being 2.34 (CI 1.39-3.93, p=0.0014), 1.76 (1.20-2.58, p=0.0035), and 1.5 (CI 1.18-2.01, p=0.0016) ( Figure ). Conclusions: The risk for VTE conferred by the FVL variant appears to decline with age. This finding may help to better identify individuals who would most benefit from FVL screening.
Published Version
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