There is a substantial gap between SNP-alcohol dependence associations and understanding how these SNPs contribute to alcohol dependence. The functional effects of SNPs on alcohol dependence can be mediated through several mechanisms. Variation in gene expression is an important mechanism underlying susceptibility to alcohol dependence. The abundance of a gene transcript is directly modified by polymorphism in regulatory elements. Consequently, transcript abundance might be considered as a quantitative trait that can be mapped with considerable power, which has have been named expression QTLs (eQTLs). To examine the relationships between all risk SNPs (listed in Table 1) and mRNA expression levels of the proximate protein-coding genes, we examined the expression data in human lymphoblastoid cell lines from 270 unrelated HapMap individuals including six different populations (14), in 93 autopsy-collected frontal cortical brain tissue samples with no defined neuropsychiatric condition, and in 80 peripheral blood mononuclear cell (PBMC) samples collected from living healthy donors (15). The expression data were normalized across all samples for a tissue type (four separate normalizations) per Affymetrix PLIER protocol with a sketch-quantile normalization procedure (Affymetrix Expression Console).
