MicroRNAs modify relationships between hemoglobin A1c and race and ethnicity

AIMS: To identify microRNAs that modify associations between categories of race and ethnicity and HbA1c, and to identify associated extrinsic factors and biological mechanism through which this modification may occur. METHODS: This study was a secondary analysis of the DPP trial, featuring 1000 participants with microRNA data available at baseline, and a subset of 150 with longitudinal microRNA data. Modification of relationships between categories of race and ethnicity and HbA1c by microRNAs were assessed cross-sectionally with linear models, and longitudinally with linear mixed models. In-silico analyses were performed to identify target mRNAs and pathways of identified modifying miRs. Linear models were used to assess for relationships between socioenvironmental variables and modifying miRs in an exploratory analysis. RESULTS: we identified one microRNA that modified associations between categories of race and ethnicity and HbA1c at baseline (miR-29b) and two that showed longitudinal modifications (miR-92a, miR-146a). MiroRNAs that modified relationships between HbA1c and categories of race and ethnicity were also associated with socioenvironmental factors including nutrition, income, education, and exercise in exploratory models. CONCLUSIONS: We identified microRNAs that modify associations between self-reported categories of race and ethnicity and HbA1c, potentially reflecting confounding of theses associations by socioenvironmental factors, geographic ancestry, and other individual-level characteristics.