SNP Set Association Testing for Survival Outcomes in the Presence of Intrafamilial Correlation

In this work, we propose a single nucleotide polymorphism (SNP) set association test for censored phenotypes in the presence of a family‐based design. The proposed test is valid for both common and rare variants. A proportional hazards Cox model is specified for the marginal distribution of the trait and the familial dependence is modeled via a Gaussian copula. Censored values are treated as partially missing data and a multiple imputation procedure is proposed in order to compute the test statistics. The P‐value is then deduced analytically. The finite‐sample empirical properties of the proposed method are evaluated and compared to existing competitors by simulations and its use is illustrated using a breast cancer data set from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2.