Many of the reported genetic variants have been identified through single SNP association tests. Despite many of the successes, a single SNP tends to have a small effect, and the single SNP-based association tests require a very stringent significance level, which is likely a key factor to the so-called “missing heritability” problem [48, 49]. To overcome some of these limitations, gene-based analysis [50–52] has emerged to jointly analyze the SNPs within genes. Gene-based methods are less affected by the heterogeneity of a single locus; hence the results may be more robust across populations [53], which increases the likelihood of replication. Hence, we performed both single SNP-based and gene-based association analyses for the data from the Study of Addiction: Genetics and Environment (SAGE) [6] which includes well-characterized phenotypic data on substance dependence including addiction to nicotine, alcohol, marijuana, cocaine, opiates, and other drugs. In our analysis, we find a genome-wide significant association of NCK2 gene on chromosome 2 with opiates dependence in African-origin men at both the SNP and gene levels. NCK2 is a member of NCK family of adaptor proteins,
