We tested the GxE assumption of independence between genetic risk and environment exposures (no gene – environment correlation) by estimating the association between the SNPs rs16969968, rs578776, rs13277254, rs12466358 and peer smoking among controls only [30]. There was no evidence of such rGE between any SNP and H.S. peer smoking using a negative binomial regression model [31] (Incident Risk Ratios: 0.99 to 1.02, p-values > 0.30 for all SNPs). Although the lack of a correlation between these SNPs and H.S. peer smoking might suggest use of a case only approach to testing GxE interactions, we retained use of the case-control method to avoid the potential increase in Type 1 error [30]. The absence of rGE in the control only analyses provides some evidence that any observed GxE interaction is unlikely to be attributable to rGE in the population.
