Genetic influences on peripheral arterial disease in a twin population.

OBJECTIVE To analyze the contribution of genetic and environmental factors to the development of peripheral arterial disease (PAD) in a large population-based sample of twins. METHODS AND RESULTS The understanding of genetics in PAD is still limited. From the Swedish Twin Registry and the national patient discharge registry, 1464 twins with PAD were identified, including 33 monozygotic (MZ) and 42 dizygotic (DZ) concordant pairs and 298 MZ and 1008 DZ discordant pairs. Traditional cardiovascular risk factors were significantly more prevalent in twins with PAD than in those without PAD. Concordances and correlations were higher in MZ compared with DZ twins, indicating genetic influences in PAD. The risk of PAD for persons whose twin had PAD compared with persons whose twin did not have PAD, estimated as an odds ratio, was 17.7 (95% CI, 11.7 to 26.6) for MZ twins and 5.7 (95% CI, 4.1 to 7.9) for DZ twins. In the structural equation models, Mx analyses, genetic effects accounted for 58% (95% CI, 50% to 64%) and nonshared environmental effects for 42% (95% CI, 36% to 50%) of the phenotypic variance among twins. CONCLUSIONS Heritability is an important component, along with unique environmental factors, for the development of PAD. The proportion of the overall PAD heritability attributed to the heritability of cardiovascular risk factors needs to be resolved. Traditional risk factors could explain a major proportion of PAD heritability. A better understanding of the genetics in PAD could identify individuals at increased risk who may benefit from targeted therapies.