The second approach involves genetic association in population and/or family-based samples. Genetic association is essentially a form of linkage mapping but is allele-based rather than locus-based (Table 1). Association studies identify alleles of a gene that are more or less common in people with a trait or disease versus those without. COGA has conducted several candidate-gene association studies and found association with more than 20 genes affecting both alcohol dependence and endophenotypes associated with alcoholism (Edenberg and Foroud, 2006). Other similar studies by investigators all over the world, in a range of different populations, have identified genetic variants that contribute towards vulnerability to alcoholism (Goldman et al., 2005a; Kalsi et al., 2009). In this group of genes almost all of the major neurotransmitter systems are represented including: GABA, glutamate, serotonin, dopamine, and acetylcholine. Genes involved with alcohol metabolism (alcohol dehydrogenase [ADH] and aldehyde dehydrogenase [ALDH]) as well as neuropeptide signaling (neuropeptide Y [NPY], corticotropin-releasing hormone [CRH]), neuroendocrine signaling, other signaling molecules (multiple PDZ domain protein [MPDZ]), and cellular architecture (ras suppressor protein 1[RSU1]) are also implicated (Edenberg and Foroud, 2006; Kranzler and Edenberg, 2010).
