ISTH Academy

Data on the proportion of venous thromboembolism (VTE) risk attributed to prothrombotic genotypes in men and women are limited.

We aimed to estimate the population attributable fraction (PAF) of VTE for recognized, common prothrombotic genotypes in men and women using a population-based case cohort.

Cases with incident VTE (n = 1493) and a randomly sampled subcohort (n = 13,069) were derived from the Tromsø study (1994-2012) and the Trøndelag Health Study (1995-2008) cohorts. DNA samples were genotyped for 17 single-nucleotide polymorphisms (SNPs) previously associated with VTE. PAFs with 95% bias-corrected CIs (based on 10,000 bootstrap samples) were estimated for SNPs significantly associated with VTE, and a 6-SNP cumulative model was constructed for both sexes.

In women, the individual PAFs for SNPs included in the cumulative model were 16.9% for ABO (rs8176719), 17.6% for F11 (rs2036914), 15.1% for F11 (rs2289252), 8.7% for FVL (rs6025), 6.0% for FGG (rs2066865), and 0.2% for F2 (rs1799963). The cumulative PAF for this 6-SNP model was 37.8%. In men, the individual PAFs for SNPs included in the cumulative model were 21.3% for ABO, 12.2% for F11 (rs2036914), 10.4% for F11 (rs2289252), 7.5% for FVL, 7.8% for FGG, and 1.1% for F2. This resulted in a cumulative PAF in men of 51.9%.

Our findings in a Norwegian population suggest that 52% and 38% of the VTEs can be attributed to known prothrombotic genotypes in men and women, respectively.

• Sex-specific data on venous thrombosis risk attributed to prothrombotic genotypes are scarce. • We estimated the cumulative population attributable risk of 6 single-nucleotide polymorphisms in men and women. • For this 6-single-nucleotide polymorphism model, the cumulative population attributable risk was 51.9% in men and 37.8% in women. • Prothrombotic genotypes appeared to explain a higher proportion of venous thromboses in men than in women.