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SNP Set Association Testing for Survival Outcomes in the Presence of Intrafamilial Correlation
Author(s) -
Leclerc Martin,
Simard Jacques,
LakhalChaieb Lajmi
Publication year - 2015
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.21914
Subject(s) - imputation (statistics) , statistics , snp , single nucleotide polymorphism , proportional hazards model , mathematics , copula (linguistics) , correlation , censoring (clinical trials) , missing data , biology , genetics , econometrics , genotype , gene , geometry
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.