An ongoing study of these nicotinic receptor variants57 illustrates an important issue concerning phenotypic assessment. Using reports of CPD, the statistical signal detected for SNP rs16969968—although highly significant with very large samples—is small. But when this genetic variant is instead used to predict concentrations of serum cotinine (a long-lasting metabolite of nicotine), the association becomes much stronger. Presumably this difference arises because self-reports of CPDs are a poor measure of the amount of nicotine absorbed. This study may provide important lessons for studies of other SUDs. The power of genetic analysis is closely intertwined with the quality of the phenotypic measures.
