Furthermore, similar to the observation on chromosome 15, the chromosome 8 locus is associated with opposing effects on the risk for cocaine dependence and nicotine dependence. The CHRNB3-A6 locus is associated with decreased risk for nicotine dependence and increased risk for DSM-5 cocaine use disorder. In contrast, in CHRNA5, the same variant, D398N (rs16969968), increases risk for nicotine dependence and decreases risk for cocaine dependence. Furthermore, our data suggest that different but overlapping SNPs may explain the cocaine and nicotine dependence associations in CHRNB3-A6 rather than a single SNP causing opposing effects as was seen on chromosome 15. These results suggest that CHRNA5 and CHRNB3-A6 demonstrate pleiotropic effects on substance dependence risk.
