Individuals with call rates <90% and SNPs with minor allele frequency MAF <1% were excluded from the analysis. The P value for the Hardy-Weinberg equilibrium was set up by >0.0001. These steps reduced the level of noise in genotypes and increased the efficiency of analysis. There are 60 duplicate genotype samples and 9 individuals with ethnic backgrounds other than African origin or European origin. All of those individuals were removed from the subject list. Finally, there were a total of 3,627 unrelated samples with 859,185 autosomal SNPs for our final analysis. To alleviate the confounding by population substructure, we stratified the sample by race and sex. Finally, there are four sub-samples: 1,393 European-origin women, 1,131 European-origin men, 568 African-origin women and 535 African-origin men. The distribution of subjects diagnosed with lifetime dependence on substances in each of the six categories: nicotine, alcohol, marijuana, cocaine, opiates, or other drugs are presented in Table 1.
