Genetic associations have been established for CHRNA5/A3/B4 polymorphisms with cigarette smoking(Saccone et al., 2007; Thorgeirsson et al., 2010) and cocaine dependence,(Grucza et al., 2008; Sherva et al., 2010) and ADH1B and ALDH2 polymorphisms with alcohol dependence.(Frank et al., 2012; Gelernter et al., 2014a; Park et al., 2013; Quillen et al., 2014) Other plausible genetic associations for drug abuse behaviors have been identified but have not been conclusively replicated.(Wang et al., 2012) One challenge to identifying genetic polymorphisms contributing to drug abuse has been development of large sample sizes for genome-wide association studies (GWAS). The largest prior GWAS (N=3,318 African Americans [AAs] and 2,379 European Americans [EAs]) identified significant single nucleotide polymorphism (SNP) associations with opioid (Gelernter et al., 2013) or cocaine dependence (Gelernter et al., 2014b), which await independent replication. Other GWAS of drug abuse behaviors, containing up to 3,053 subjects, identified only nominally significant SNP associations.(Agrawal et al., 2014; Liu et al., 2013; Nielsen et al., 2010; Uhl et al., 2008) In this study, we assembled a cohort of 10,587 subjects (3,742 AAs and 6,845 EAs) to conduct the
