Since the ND or FTND cases included in our samples are affected with other substance dependence disorders, including cocaine dependence (CD), alcohol dependence (AD) and/or opioid dependence (OD), we also investigated whether the signals associated with smoking behavior could be driven by other substance dependence disorders. To control the effect of other substance dependence disorders, we reanalyzed the data by including CD, AD and OD status as covariates in the regression model. As a result, rs2236196 remained significant for CPD (P = 0.0078) and was less significant for ND (P = 0.042). However, the signal disappeared for rs1044394 for both ND and FTND. We speculate that this loss of a signal for rs1044394 is attributable to either random fluctuation or that other substance dependence disorders drive the association between rs1044394 and ND (or FTND). It will be necessary to examine the role of CHRNA4 in other substance dependence disorders to determine the basis for this finding.
