FAMILIAL AGGREGATION STUDIES WITH MATCHED PROBAND SAMPLING

A method is proposed for the analysis of clustered, continuous data ar ising from matched familial aggregation studies. The problem is sugges ted by a study designed to estimate the familial aggregation of obstru ctive sleep apnea (OSA). The study design uses 'proband' sampling, in which individuals identified at sleep clinics as having a high degree of OSA ('cases') are matched to neighborhood 'controls', individuals w ith normal levels of OSA. The resulting data are used to develop estim ates of familial correlations for indices of hypopnea/apnea derived fr om the sleep monitoring of individual family members. The properties o f conditional multivariate normal distributions and random-effects mod els are used to accommodate proband sampling and matching effects. Exa mples and simulations are used to demonstrate the importance of applyi ng the proposed procedures.