Our results are compatible with negative results from prior genome-wide meta-analyses of cigarettes-per-day (Liu et al. 2010; The Tobacco and Genetics Consortium 2010; Thorgeirsson et al. 2010). Our hypothesis-driven analyses of a single SNP translate to a study-wide required significance threshold of 9.76×10−3. This led to statistically significant evidence for a modest effect (OR=0.90) of rs1799971 on general substance dependence liability, in N=16,908 subjects (Table 3). The three genome-wide smoking consortia tested OPRM1 only in each consortium separately (N=38,000, N=31,000, and N=16,000 smokers with cigarettes-per-day); estimated power to have detected the nicotine-specific odds ratio of 0.93 (Table 3) in at least one of the three consortia with genome-wide significance (alpha=5×10−8) is only 4%. Power details are in Supplementary Text S2. Hence it is not surprising that these smoking consortia did not report an OPRM1 effect.
