Efficient Genome-Wide Association Testing of Gene-Environment Interaction in Case-Parent Trios
Year: 2010
Type: article
Abstract: 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.
Source: American Journal of Epidemiology
DOI: 10.1093/aje/kwq097
Institution: University of Southern California
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: Factors in Childhood Lung Susceptibility to Pollution, Environmental Genomics, A Genome-wide Association Study of Childhood Respiratory Outcomes, Genetics, Air Pollution, and Respiratory Effects in Children and Young Adults, G3180148751, Air Pollution and Preclinical Atherosclerosis in Elementary-School Children, Air Pollution, Intima-media Thickness, and Lung Function in College Students, Air Pollution, Inflammation and New Onset Asthma, Methods for Pathway Modeling with Application to Folate, G6390881565, Children's Environmental Health Center, Genomic Analysis of the genotype-phenotype map, Environmental Exposures, Host Factors and Human Disease
OpenAlex ID: W2122047719