Genetic liability to alcohol dependence is likely to be substantially attributable to many variants, each contributing in only a small amount to the overall genetic risk. When many markers are examined separately for association with a complex trait, genuine genetic effects reflected by individual markers may be too small to overcome significance thresholds that account for multiple testing. However, the aggregated effects of multiple individually insignificant SNP markers combined into a single polygenic score may be associated with phenotypic variation (International Schizophrenia Consortium, 2009). For example, a similar approach has been used to calculate a score from multiple SNPs in dopamine system genes, which accounted for a small but significant percentage of variance in cocaine dependence symptomatology (Derringer et al., 2012).
