We constructed wGRS using the independent 19q13.2 SNPs and tested whether the wGRS predicts smoking behavior in two independent Finnish samples. The wGRS constructed of major alleles (increasing the metabolism rate) was associated with increased smoking quantity. This is in line with previous evidence of faster metabolizers smoking more [66]. Adding the rs56113850*rs113288603 interaction term to the wGRS analyses did not improve model fit, suggesting that the simpler model with main effects was sufficient. Our unadjusted wGRS results for current vs. former smoking suggested that major alleles that associate with faster metabolism associate with increased odds of being a former smoker; after adjustment and exclusion for potential confounders the wGRS result no longer was significant. Although the sample size decreased, the confidence intervals did not significantly increase, suggesting that the change in results is due to reduced confounding rather than reduced power. Many clinical trials and epidemiological studies indicate that slow metabolizers quit more often than normal metabolizers [20, 67, 68]. Possibly our wGRS does not capture all the relevant aspects of measured NMR or the cross-sectional nature of the FINRISK smoking status data did not permit us to fully replicate earlier findings.
