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Chunk #22 — Results — Gene expression predicts functional differences between KCNJ6 haplotypes

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Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons.
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genes (Supplementary Table 5) are synaptic signaling and neuro projection morphogenesis. Up-regulated genes (Supplementary Table 4) predict functions associated with protein targeting within the cells, catabolic metabolism, and nonsense-mediated decay. KCNJ6 mRNA trended lower in untreated AF than in UN (Fig. 1C; p = 3.15 × 10–5 by LRT over both genotype and ethanol treatment; p = 0.0508 for untreated AF vs. UN by Wald test). Interestingly, 7 d of IEE increased levels of KCNJ6 mRNA (Fig. 1C; p = 0.0225, Wald test) so that the treated AF group was no longer different from untreated UN (p = 0.322; Wald test). Analysis by sex identified no significant differences in KCNJ6 mRNA. Results indicate that the variant KCNJ6 haplotype leads to differential expression of GIRK2 and that ethanol exposure will reverse these effects.