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). Using the same analytic strategies as previously published (Zuo et al., 2011, 2012), we performed cis-acting expression of quantitative locus (cis-eQTL) analysis on the risk SNPs in lymphoblastoid cell lines (Stranger et al., 2005), brain tissues and peripheral blood mononuclear cell (PBMC) samples (Heinzen et al., 2008). We also performed transcriptome-wide trans-eQTL analysis on the risk SNPs (α=2.4×10−8), genome-wide trans-eQTL analysis of NKAIN1-SERINC2 transcript expression (α=4.7×10−8), and transcriptome-wide expression correlation analysis (α=3.4×10−7) in brain tissues and PBMC samples (Heinzen et al., 2008; Table 3, Tables S3, S4 and S59, and Figure 1).
