Project.1 We performed genome-wide miRNAs profiling and tested the causal associations between miRNAs and type 2 diabetes in the general population. The associations of 591 well-expressed miRNAs with prevalent and incident type 2 diabetes were examined. Mendelian Randomization (MR) was conducted to investigate the causal associations and miRNA-target genes and metabolites were studied in relation to type 2 diabetes. At baseline, higher plasma levels of miR-139-5p and miR-193a-5p were associated with prevalent type 2 diabetes. During a follow-up of >9.0 years, 209 participants developed type 2 diabetes, in which plasma levels of miR-99a-5p, miR-4664-3p, miR-29a-3p, miR-122-5p, and miR-125b-5p were significantly associated with incident type 2 diabetes. MR confirmed a causal effect for miR-139-5p on type 2 diabetes. We found several target genes and metabolites that could link miR-139-5p to pathways underlying type 2 diabetes.

MiR-139-5p is a causal biomarker for type 2 diabetes; Results from genome-wide microRNA profiling and Mendelian randomization analysis in a population-based study. Mens M,…, Ghanbari M. medRxiv 2021.05.13.21257090; doi: https://doi.org/10.1101/2021.05.13.21257090