In the present study, we searched for significant risk genomic regions for alcohol and nicotine co-dependence using a GWAS. A European-American cohort was used as the discovery one, and a European-Australian cohort and an African-American cohort were used as the replication ones. Additionally, we used three independent samples of European descent to detect expression quantitative trait locus (eQTL) signals in this risk genomic region, to see if the risk variants were functional. Finally, as contrast, we tested gene-disease associations in 18 additional independent cohorts with 10 other non-alcoholism neuropsychiatric disorders, to see whether the risk regions were specific for alcohol and nicotine co-dependence or not.