Modeling Familial Association of Ages at Onset of Disease in the Presence of Competing Risk

Summary In genetic family studies, ages at onset of diseases are routinely collected. Often one is interested in assessing the familial association of ages at the onset of a certain disease type. However, when a competing risk is present and is related to the disease of interest, the usual measure of association by treating the competing event as an independent censoring event is biased. We propose a bivariate model that incorporates two types of association: one is between the first event time of paired members, and the other is between the failure types given the first event time. We consider flexible measures for both types of association, and estimate the corresponding association parameters by adopting the two-stage estimation of Shih and Louis (1995, Biometrics 51, 1384–1399) and Nan et al. (2006, Journal of the American Statistical Association 101, 65–77). The proposed method is illustrated using the kinship data from the Washington Ashkenazi Study.