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Chunk #39 — Discussion — Noncoding KCNJ6 polymorphisms in AUD

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Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons.
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In addition to the three synonymous and intronic SNPs used to select subjects (Table 1), examination of variants in the long 3′UTR by RNAseq alignment predicts linkage of 19 additional SNPs (Fig. 1B; Supplementary Table 1). None of the 3′ UTR SNPs could be mapped uniquely to known regulatory sequences such as predicted microRNA target sites. That is, some SNPs are predicted to destroy or add predicted targeting sites, but all were found in multiple locations within the 3′ UTR, not only where they might be altered by a SNP. It is possible, however, that altered microRNA targeting of one or more sites among many in the 3′UTR could play a role in regulating the stability or translation of the variant KCNJ6 mRNA, but no clear candidates could be identified for testing.