Subjects were selected from among previously described samples, Yale-Penn 1 (n = 5540) and 2 (n = 3675)6, which were recruited from five eastern US sites to participate in studies of the genetics of drug (opioid or cocaine) or alcohol dependence6. All participants were given written informed consent that was approved by the institutional review board at each recruiting site. Certificates of confidentiality were provided by the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. Yale-Penn 1 samples were genotyped on the Illumina (San Diego, CA, USA) HumanOmni1-Quad v1.0 microarray. A total of 1,140,419 single-nucleotide polymorphisms (SNPs) were genotyped in Yale-Penn 1. Samples for Yale-Penn 2 were genotyped with the Illumina HumanCore Exome array, which includes a total of 550,601 SNPs, including 268,631 exonic SNPs and 281,970 tagging SNPs. Quality control (QC) for microarrays in each cohort was carried out using PLINK1.97 based on the following criteria: (1) individual genotype missing rate < 2%, (2) SNP genotype missing rate < 2%, (3) Hardy–Weinberg P > 1 × 10−6, and (4) minor allele frequency (MAF)