Background The proportion of venous thromboembolism (VTE) events that can be attributed to established prothrombotic genotypes has been scarcely investigated in the general population. We aimed to... Show moreBackground The proportion of venous thromboembolism (VTE) events that can be attributed to established prothrombotic genotypes has been scarcely investigated in the general population. We aimed to estimate the proportion of VTEs in the population that could be attributed to established prothrombotic genotypes using a population-based case-cohort. Methods Cases with incident VTE ( n = 1,493) and a randomly sampled subcohort ( n = 13,069) were derived from the Tromso Study (1994-2012) and the Nord-Trondelag Health (HUNT) study (1995-2008). DNA samples were genotyped for 17 single-nucleotide polymorphisms (SNPs) associated with VTE. Hazard ratios with 95% confidence intervals (CIs) were estimated in Cox regression models. Population-attributable fractions (PAFs) with 95% bias-corrected CIs (based on 10,000 bootstrap samples) were estimated using a cumulative model where SNPs significantly associated with VTE were added one by one in ranked order of the individual PAFs. Results Six SNPs were significantly associated with VTE (rs1799963 [Prothrombin], rs2066865 [FGG], rs6025 [FV Leiden], rs2289252 [F11], rs2036914 [F11], and rs8176719 [ABO]). The cumulative PAF for the six-SNP model was 45.3% (95% CI: 19.7-71.6) for total VTE and 61.7% (95% CI: 19.6-89.3) for unprovoked VTE. The PAF for prothrombotic genotypes was higher for deep vein thrombosis (DVT; 52.9%) than for PE (33.8%), and higher for those aged <70 years (66.1%) than for those aged >= 70 years (24.9%). Conclusion Our findings suggest that 45 to 62% of all VTE events in the population can be attributed to known prothrombotic genotypes. The PAF of established prothrombotic genotypes was higher in DVT than in PE, and higher in the young than in the elderly. Show less
Background Family history of myocardial infarction (FHMI) is known to increase the risk of venous thromboembolism (VTE). Objectives To investigate the effect of prothrombotic genotypes on the... Show moreBackground Family history of myocardial infarction (FHMI) is known to increase the risk of venous thromboembolism (VTE). Objectives To investigate the effect of prothrombotic genotypes on the association between FHMI and VTE in a case-cohort recruited from a general population. Methods Cases with a first VTE (n = 1493) and a subcohort (n = 13 072) were sampled from the Tromso study (1994-2012) and the Nord-Trondelag health (HUNT) study (1995-2008). The DNA samples were genotyped for rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11). Participants with missing information on risk alleles (n = 175), FHMI (n = 2769), and BMI (n = 52) were excluded. Cox regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for VTE. To explore the role of prothrombotic genotypes for the association between FHMI and VTE, we (a) included the genotypes in the multivariable-adjusted models and (b) assessed the joint effects between FHMI and genotypes on VTE risk. Results The FHMI was associated with a 1.3-fold increased risk of VTE (HR 1.32, 95% CI 1.16-1.50) and 1.5-fold increased risk of unprovoked VTE (HR 1.47, 95% CI 1.22-1.78). The risk of VTE by FHMI did not alter after adjustment for the five genotypes. The combination of FHMI and the different prothrombotic genotypes did not result in an excess VTE risk (i.e. no biological interaction). Conclusions Our findings suggest that the risk of VTE by FHMI is not explained by rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11). The combination of FHMI with prothrombotic genotypes had an additive effect on VTE risk. Show less
