Major Genetic Susceptibility for Venous Thromboembolism in Men: A Study of Danish Twins

Background. Although several genetic determinants (mutations or polymorphisms) have been associated with increasedrisk of venous thromboembolism, the overall influence of genetic factors on this disease is unknown.Methods. We linked the Danish Twin Registry, which includes twins born 1870–1953, with the Danish National Registry of Patients, comprising all hospitalizations in Denmarksince 1977. We then determined the risk of venous thromboembolism as determined from discharge diagnosis.Results. We identified 26,982 twins who were alive on 1January 1977, and computed measures of familial and geneticassociation of venous thrombotic disorders. Individuals wereclassified according to zygosity and hospitalization with venousthromboembolism. Since 1977, 678 twins were hospitalizedwith an episode of venous thromboembolism. Of these, only545 pairs (281 male pairs and 264 female pairs) were alive in1977. For men, the concordance rates for mono- and dizygotictwin pairs, respectively, were 0.22 (95% confidence interval 0.14 to 0.30) and 0.08 (0.04–0.12). The odds ratio (interpreted as the relative risk of venous thromboembolism for onetwin, given venous thromboembolism in the partner twin) was13.5 (7.3–24.8) among monozygotic twins and 3.8 (1.8–8.3)among dizygotic twins. The respective correlations for venousthromboembolism were 0.55 (0.38–0.70) and 0.26 (0.09–0.42). The proportion of the variance attributable to geneticeffects on venous thromboembolism in males was 55% (39%–68%). The remaining variation could be attributed to men’snonfamilial environments. In contrast, for women there wasno intra–twin pair similarity for venous thromboembolism.Conclusions. We found differences in genetic susceptibility tovenous thromboembolism between the sexes, with geneticfactors playing a substantially stronger role in males than infemales