In association analyses, genetic variants are examined for whether a particular version or versions increase risk for a phenotype. There are many different types of genetic variation, including single nucleotide variation and structural variation (e.g., insertions, inversions, deletions, duplications, and copy-number variants). Single nucleotide polymorphisms (SNPs), which are single-nucleotide substitutions of one base (adenine, thymine, guanine, or cytosine) for another, are the most common type of genetic variation. Hypothesis-free association analyses can be used to fine-map an area of interest identified through linkage to more precisely locate the source of a genetic signal. In an example of this from the COGA sample, chromosome 2—for which there was earlier evidence of linkage to alcohol dependence (Foroud et al., 2000), conduct disorder (Dick et al., 2004), and suicidality (Hesselbrock et al., 2004)—was fine-mapped for association using a combined phenotype of alcohol dependence with conduct disorder or suicidality (Dick et al., 2010). In total, 23 genes on chromosome 2 were associated with this combined phenotype.
