In conclusion, we observed evidence of association between cotinine levels in current smokers and a locus at 4q13.2 encompassing UGT2B10, which encodes an enzyme playing a key role in nicotine and cotinine glucuronidation, in addition to the 15q25.1 region, previously shown to robustly associate with smoking quantity. Our analyses clearly illustrate the benefit of using precise, objective phenotypes in GWAS. However, they also importantly illustrate that biomarkers do not always capture the phenotype of interest. The use of metabolite data (such as cotinine) as a proxy for environmental exposures should be carefully considered in the context of individual differences in metabolic pathways.
