Another locus was rs2677485 near NR4A2 (also known as NOT; RNR1; HZF-3; NURR1; TINUR) at 2q24.1. Although it was at the marginal significant association level in the meta-analysis (p=5.5×10−7), two other SNPs (rs4407211 with p=3.24×10−6 and rs13035632 with p=6.11×10−6) were also reported in the top identified SNPs. In addition, NR4A2 had the most flanking SNPs that were replicated in the OZALC sample and a total of 12 loci were confirmed in the replication study (Table 4). Cis-eQTL signal was also detected in this gene. NR4A2 was an orphan nuclear receptor transcripts factor that appeared to be predominantly brain-specific and expressed in dopaminergic neurons (Zetterstrom et al., 1996). Interestingly, Werme et al. (Werme et al., 2003) reported the involvement of NR4A2 in the transition to a state of high ethanol consumption as well as in the development of a high amount of wheel running in mice. Findings of NR4A2 variation have been reported to be associated with nicotine and AD (Bergen et al., 2009; Ishiguro et al., 2002).
