The influence of smoking and BMI on heritability in susceptibility to coronary heart disease

Cause-specific mortality data on Danish monozygotic (MZ) and dizygotic (DZ) twins are used to analyze the influence of smoking and body mass index (BMI) on heritability estimates of susceptibility to coronary heart disease (CHD). The sample includes 1209 like-sexed twin pairs born between 1890 and 1920, where both individuals were still alive and answered a questionnaire, including information about smoking, height and weight, in 1966. The analysis was conducted with both sexes pooled due to the relatively small number of twin pairs. Follow-up was conducted from 1 January 1966 to 31 December 1993. We use the correlated gamma-frailty model with observed covariates for the genetic analysis of frailty to account for censoring and truncation in the lifetime data. During the follow-up, 1437 deaths occurred, including 435 deaths due to CHD. Proportions of variance of frailty attributable to genetic and environmental factors were analyzed using the structural equation model approach. Different standard biometric models are fitted to the data to evaluate the magnitude and nature of genetic and environmental factors on mortality. Using the best fitting model without covariates, heritability of frailty to CHD was found to be 0.45 (0.11). This result changes only slightly to 0.54 (0.16) after controlling for smoking and BMI. This analysis underlines the existence of a substantial genetic influence on individual frailty associated with mortality caused by CHD. No evidence for common genetic factors acting on smoking, BMI, and susceptibility to CHD are found which indicates that the association between smoking and susceptibility to CHD and BMI and susceptibility to CHD is not confounded by common genetic factors