Genetic influences on CHD-death and the impact of known risk factors: comparison of two frailty models

The importance of some recognized risk factors on genetic influences for coronary heart dis-ease (CHD) needs further clarification. The aim of the present study was therefore to study the impact of known risk factors on genetic influences for CHD-death. Both twin (corre-lated gamma-frailty) and non-twin models (univariate gamma-frailty) were utilized and compared regarding their suitability for genetic analyses. The study population consisted of twins born in Sweden between 1886 and 1925. As expected, our findings indicate that genetic influences are important for CHD-death. Inclusion of risk factors in the twin-model increased heritability estimates, primarily due to a substantial reduction in non-shared envi-ronmental variances. The genetic influences for CHD-death are only marginally mediated through the risk factors among males, but more so among females. Although the outcome phenotype used in the present study is not behavioral, the analyses demonstrate the poten-tial of frailty models for quantitative genetic analyses of categorical phenotypes. KEY WORDS: Coronary heart disease; frailty; heritability; risk factors; twins