We have shown, in genotyped data from European-Americans in the SAGE dataset, that there are at least two statistically independent signals associated with increased risk for DSM-5 cocaine use disorder in the region of the CHRNB3-A6 nicotinic receptors on chromosome 8. Several SNPs representing the rs9298626 LD bin surpass the multiple test correction for the region with DSM-5 cocaine use disorder (p = 0.002). rs9298626 is also associated with reduced risk for nicotine dependence (OR = 0.47, 95% CI = 0.30–0.76, p = 1.80 × 10−3) in a univariate genetic analysis. This may be due in part to the fact that, in European ancestry populations, the minor allele of rs9298626 (MAF = 0.04) occurs almost exclusively on the background of the more frequent minor allele (MAF = 0.22) for rs1451240 previously reported to be genome-wide significantly associated with nicotine dependence (Table 3). Conditioning on rs1451240 had no effect on the association with DSM-5 cocaine use disorder (Table 5). This is not surprising because rs1451240 is not associated with DSM-5 cocaine use disorder in our data (Table 1).
