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Two‐stage analysis for gene‐environment interaction utilizing both case‐only and family‐based analysis
Author(s) -
Chen YiHau,
Lin HuiWen,
Liu Huimei
Publication year - 2009
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.20357
Subject(s) - stage (stratigraphy) , biology , genetics , gene , computational biology , paleontology
Abstract 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. Genet. Epidemiol . 2008. © 2008 Wiley‐Liss, Inc.