Overall, the convergence of evidence supports a region on chromosome 11 as the strongest candidate. It contained many of the top SNPs from the case control sample, and several SNPs genotyped in the family sample support the association of this region with alcohol dependence and the early onset of dependence (Table 2; Figure 2A,B; Supplementary Table 1). This region contains 6 genes: SLC22A18 (solute carrier family 22, member 18, a poly-specific organic cation transporter), PHLDA2 (pleckstrin homology-like domain, family A, member 2, important in regulating placental growth), NAPIL4 (nucleosome assembly protein 1-like 4, a likely histone chaperone), CARS (cysteinyl-tRNA synthetase), OSBPL5 (oxysterol-binding protein-like protein 5, an intracellular lipid receptor that interacts with retinoic acid and estradiol), and SNORA54 (small nucleolar RNA, H/ACA box 54). The four genes that were assayed (PHLDA2, NAPIL4, CARS, OSBPL5) are expressed in the human brain. In LCLs, expression of SLC22A18 and PHLDA2 are increased 9-14% by ethanol exposure (FDR < 0.05), while expression of NAP1L4 is decreased 8% by ethanol (FDR <10−5; Edenberg et al., in preparation). These lines of evidence suggest that one or
