We conducted a meta-analysis of genome-wide association data on cotinine levels in current smokers, in order to identify genetic variants associated with smoking behaviour. We identified 375 genetic variants, representing three independent signals. Two of these signals were located within CHRNA5-A3-B4 on chromosome 15, a region that is now well-established as being associated with smoking heaviness. More importantly however, we also identified a signal within UGT2B10 on chromosome 4, a locus which has previously been found to associate with cotinine and nicotine metabolism, but not with nicotine dose, highlighting an important limitation of the use of metabolite data (such as cotinine) as a proxy for an environmental exposure.
