Of note, the literature on GABRA2 has largely focused on single nucleotide polymorphisms (SNPs) within two complementary (yin–yang) GABRA2 haplotypes that account for most of the haplotype diversity in Caucasians and Asians [4]. Major, or more frequent, alleles of SNPs within this haplotype block tag the major haplotype and vice versa in these populations. There is some inconsistency regarding which is the risk allele/haplotype from these yin–yang haplotypes and SNPs within them. For example, for the well-studied polymorphism, rs279858 (see “Methods” for more detail), some studies found that the major (A) allele predicted risk for externalizing-related problems [15, 20, 28]. However, others found that the minor (G) allele predicted risk for externalizing phenotypes such as conduct and alcohol problems in predominantly Caucasian samples [12, 16, 23, 24, 29]. Similar inconsistent findings have been observed for other SNPs in the haplotype block and externalizing disorders [17, 19, 21]. Interestingly, one study showed that alcoholics with high trait anxiety had a higher abundance of the major haplotype, while alcoholics with low trait anxiety had a higher abundance of the minor haplotype [69],
