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Study IDs Islet Cell MicroRNAs With Potential Ties to Diabetes

For a paper appearing in the Proceedings of the National Academy of Sciences, investigators with the National Human Genome Research Institute, the University of Cambridge, and Cornell University share findings from a microRNA-focused analysis of type 2 diabetes (T2D), uncovering human pancreatic islet (HPI) cell miRNAs with apparent ties to T2D or related traits. We describe the genetic regulation of HPIs miRNA expression and provide insight into the role of miRNAs in T2D pathophysiology," the authors write. After performing RNA sequencing, genotyping, and/or small RNA sequencing on islet cell samples from 69 HPI samples, the team profiled miRNA expression and regulation in samples from 63 genotyped and small RNA-sequenced samples. Along with clues to miRNA heritability, the search highlighted a handful of miRNA expression quantitative trait loci (eQTL), while analyses that included expression and T2D- or glycemic trait-associated genetic locus clues helped them find 14 T2D-related miRNAs. Four more miRNAs appear to coincide with a polygenic risk score centered on levels of blood sugar and glycated hemoglobin, the investigators note. "In our genetic analysis of HPIs, we show that the expression of highly heritable miRNAs is driven primarily by trans-acting genetic effects, whereas the expression of highly heritable [messenger RNAs] is driven by a combination of cis- and trans-acting genetic effects," they write, noting that such results point to enhanced selective pressure for miRNAs, and "imply that to map miRNA-eQTLs thoroughly, large samples sizes will be required."