Most GWAS SNPs map to noncoding regions of the genome and 3.7% are found in the UTRs [47, 48]. The 3′ UTRs of transcripts expressed in brain tend to be longer than those expressed in other tissues and can be involved in post-transcriptional regulation of transcript abundance by affecting RNA stability, translation and/or localization [49, 50]. Annotation of KCNJ6 identifies two transcripts, one with a short 3′ UTR (1926 bp; ENST00000645093) and one with a substantially longer 3′ UTR (18,112 bp; ENST00000609713). RNAseq coverage analysis in human iN detects only the longer isoform, although it is possible that a relatively small portion could be the shorter isoform, but the uniformly distributed coverage (Fig. 1B) does not indicate this. This longer transcript is orthologous to a 16-kb transcript found in rat brain [51], which includes multiple AU-rich elements, which may affect mRNA stability and could be affected by KCNJ6 allelic variation. We conclude that the vast majority of KCNJ6 mRNA is consistent with having the extended 3′ UTR, with the potential for variant SNPs to affect mRNA stability or translation efficiency.
