In conclusion, our data indicate that much of the debate regarding whether the association of rs1051730–rs16969968 genotype with lung cancer is direct or operate indirectly via tobacco exposure is essentially due to imprecision in the measures of tobacco use and exposure used in most studies. More importantly, our results show that the search for even larger sample sizes in GWAS may generate diminishing returns if this is at the expense of phenotype precision. The use of objective measures of smoking behavior in genome-wide studies may reveal novel variants associated with these outcomes, which would be undetectable using conventional self-report measures.
