By extension, GWAS that rely on self-report measures to quantify smoking behavior, and therefore tobacco exposure, may be insensitive to relatively modest genetic associations. Recent studies of smoking phenotypes have enjoyed considerable success in identifying loci associated with various aspects of smoking behavior (9,20,22). Our results suggest that these studies may have underestimated the magnitude of these associations (perhaps, in particular, in the case of heaviness of smoking phenotypes). It is also likely that a number of common variants that contribute an important proportion of phenotypic variance may remain unidentified. Using biomarker phenotypes, such as cotinine, to assay nicotine consumption and tobacco exposure may improve the success of GWAS and identify additional novel variants associated with nicotine consumption.
