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 more of these genes is a good candidate for affecting the risk for alcoholism. Although not previously considered candidates for affecting the risk for alcoholism, several of these genes have functions that might relate to alcoholism, such as growth regulation, cation transport and lipid signaling. Careful dissection of a Quantitative Trait Locus (QTL) hotspot on mouse distal chromosome 1 (Mozhui et al., 2008) that includes QTLs affecting alcohol dependence (Buck et al., 2002), alcohol withdrawal (Crabbe, 1996), and alcohol induced locomotor activity (Downing et al., 2003) showed that genes located in the QTL had a trans effect on expression in nervous tissue of a set of aminoacyl tRNA synthetases (Mozhui et al., 2008). As noted by Mozhui et al. (2008), the nervous system depends heavily on finely-tuned protein metabolism in dendrites and axons (Chang et al., 2006; Malgaroli et al., 2006). Thus, CARS is a reasonable candidate.
