With rapid technological advances, there is increasing interest in moving from delineation of latent (aggregate) genetic influences to the identification of specific gene variants that may confer risk for the development of substance use disorders. The earliest genomic efforts utilized a linkage approach (see Figure 2 (panel A)). Studies applying this method identified regions on chromosome 3 and 9 for adolescent drug dependence vulnerability81 and for cannabis dependence symptoms. 82 The advantage of linkage analysis is that it allows for a parametric or non-parametric scan of the entire genome, which can, if well-powered, lead to discovery of novel genetic regions. However, these methods are often low resolution (a centiMorgan is equivalent to 1,000,000 bases of DNA, and linkage regions often span 10-50 cM). An alternative, hypothesis-focused technique is candidate gene analysis which characterizes a gene of putative biological importance with single nucleotide polymorphisms (SNPs) and compares the prevalence of the risk allele in those who are affected and unaffected (and can be related or unrelated, see panels B and C of Figure 2). SNPs are single base pair allelic variations
