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

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Abstract
Although several genetic determinants (mutations or polymorphisms) have been associated with increased risk of venous thromboembolism, the overall influence of genetic factors on this disease is unknown. We linked the Danish Twin Registry, which includes twins born 1870–1953, with the Danish National Registry of Patients, comprising all hospitalizations in Denmark since 1977. We then determined the risk of venous thromboembolism as determined from discharge diagnosis. We identified 26,982 twins who were alive on 1 January 1977, and computed measures of familial and genetic association of venous thrombotic disorders. Individuals were classified according to zygosity and hospitalization with venous thromboembolism. Since 1977, 678 twins were hospitalized with an episode of venous thromboembolism. Of these, only 545 pairs (281 male pairs and 264 female pairs) were alive in 1977. For men, the concordance rates for mono- and dizygotic twin 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 one twin, given venous thromboembolism in the partner twin) was 13.5 (7.3–24.8) among monozygotic twins and 3.8 (1.8–8.3) among dizygotic twins. The respective correlations for venous thromboembolism were 0.55 (0.38–0.70) and 0.26 (0.09–0.42). The proportion of the variance attributable to genetic effects on venous thromboembolism in males was 55% (39%–68%). The remaining variation could be attributed to men’s nonfamilial environments. In contrast, for women there was no intra–twin pair similarity for venous thromboembolism. We found differences in genetic susceptibility to venous thromboembolism between the sexes, with genetic factors playing a substantially stronger role in males than in females.