Two-stage analysis for gene-environment interaction utilizing both case-only and family-based analysis.
The case-only study and family-based study are two popular study designs for detecting gene-environment interactions. It is well known that the case-only analysis is efficient, but its validity relies crucially on the assumption of gene-environment independence in the study population. In contrast, the family-based analysis is robust to the violation of such an assumption, but is less efficient. We propose a two-stage study design for detecting gene-environment interactions, where a case-only study is performed at the first stage, and a case-parent/case-sibling study is performed at the second stage on a random subsample of the first-stage case sample as well as their parents/unaffected siblings. Statistical inference procedures are developed for the proposed two-stage study designs, which not only preserve the robustness property of the family-based analysis, but also utilize information from the case-only analysis to enhance estimation efficiency and testing power. Simulation results reveal both the robustness and efficiency of the proposed strategies.
Chen
Yi-Hau
YH
Institute of Statistical Science, Academia Sinica, Taiwan, Republic of China. yhchen@stat.sinica.edu.tw
Lin
Hui-Wen
HW
Liu
Huimei
H
D004781:Environmental Exposure; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008297:Male; D008957:Models, Genetic; D015233:Models, Statistical; D017720:Molecular Epidemiology / Q000379:methods / Q000706:statistics & numerical data