Holy Smokes—An Interaction!
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Article, see p 2336
Combining genomewide association studies in large meta-analyses has been a valuable tool for identifying genetic susceptibility loci over the past 10 years. In this issue of Circulation, Saleheen and colleagues1 use these large data sources for a deeper level analysis to identify gene by environment (G × E) interactions. The focus of their investigation is to determine whether the effects of any known coronary heart disease (CHD)-associated loci are modified by smoking behavior. At least 46 loci robustly associated with CHD have been identified to date.2
Identifying G × E interactions for CHD has been challenging given that the main effects of the known CHD-associated loci tend to be small and in aggregate account for <10% of CHD heritability.2 The remaining heritability is assumed to come from a variety of sources, including rare variants, G × G and G × E interactions, epigenetic effects, and nonadditive effects. Imprecision of environmental exposure measurements further erodes the ability to detect G × E interactions so that large sample sizes are required. In this study, the authors utilized the large CARDIoGRAMplusC4C Consortium (Coronary …