Investigation of a Candidate Gene,Environment, and G×E Interaction Using Case‐Control and Case‐Parent Study Designs

We investigated the independent contributions of a candidate gene and an environmental factor, and the presence of gene×environment (G×E) interaction, in the etiology of a disease in the Genetic Analysis Workshop (GAW) 12 problem 2 simulated data using a two‐stage approach utilizing both case‐control and case‐parent study designs. Using the case‐control design, several SNPs within candidate gene 1 (CG1) and environmental factor 1 (dichotomized using the 75^th percentile as a cut‐off) (EXP) were independently associated with disease status, in models adjusted for age and sex. We found evidence of gene×environment (G×E) interaction between EXP and two single‐nucleotide polymorphisms (SNPs) within CGI using the case‐control design. Using the case‐parent study design in the same population, we detected association between SNPs within CG1 and disease, but no G×E interaction was detected. © 2001 Wiley‐Liss, Inc.