To further examine the relationship between nicotine dependence and DSM-5 cocaine use disorder associations in this region, we performed additional conditional analyses. In a linear regression model using age, sex, study, DSM-5 alcohol symptom count, total FTND score and rs1451240 genotype as covariates, the association with DSM-5 cocaine use disorder remained significant (Table 5). Lastly, the DSM-5 cocaine use disorder signal remains significant when conditioning on the two rare variants (rs35327613 and rs149775276) recently identified by our group to be associated with DSM-IV alcohol and cocaine dependence symptom count26. This is not surprising given that these rare missense variants are present on the haplotypes containing the major allele of rs9298626, whereas the association reported here is with the minor allele. The fact that the association with cocaine use disorder remains when conditioning on the genome-wide significant signal with nicotine dependence in the region, suggests that the association is independent and not acting through nicotine dependence.
