Efficient genome-wide association testing of gene-environment interaction in case-parent trios.
Complex trait variation is likely to be explained by the combined effects of genes, environmental factors, and gene x environment (G x E) interaction. The authors introduce a novel 2-step method for detecting a G x E interaction in a genome-wide association study (GWAS) of case-parent trios. The method utilizes 2 sources of G x E information in a trio sample to construct a screening step and a testing step. Across a wide range of models, this 2-step procedure provides substantially greater power to detect G x E interaction than a standard test of G x E interaction applied genome-wide. For example, for a disease susceptibility locus with minor allele frequency of 15%, a binary exposure variable with 50% prevalence, and a GWAS scan of 1 million markers in 1,000 case-parent trios, the 2-step method provides 87% power to detect a G x E interaction relative risk of 2.3, as compared with only 25% power using a standard G x E test. The method is easily implemented using standard software. This 2-step scan for G x E interaction is independent of any prior scan that may have been conducted for genetic main effects, and thus has the potential to uncover new genes in a GWAS that have not been previously identified.
Gauderman
W James
WJ
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, 90033, USA. jimg@usc.edu
Thomas
Duncan C
DC
Murcray
Cassandra E
CE
Conti
David
D
Li
Dalin
D
Lewinger
Juan Pablo
JP
D004777:Environment; D004812:Epidemiologic Methods; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008957:Models, Genetic; D010290:Parents; D020641:Polymorphism, Single Nucleotide