Circulating metals, leukocyte microRNAs and microRNA networks: A profiling and functional analysis in Chinese adults

Background: Metals in the human body represent both environmental exposure and nutritional status. Little is known about the miRNA signature in relation to circulating metals in humans. Objectives: To characterize metal-associated miRNAs in leukocytes, individually and collectively as networks. Methods: In a panel of 160 Chinese adults, we measured 23 metals/metalloids in plasma, and sequenced miRNAs and mRNAs in leukocytes. We used linear regression to model the associations between ln-transformed metal concentrations and normalized miRNA levels adjusting for potential confounders. We inferred the enriched leukocyte subtypes for the identified miRNAs using an association approach. We utilized mRNA sequencing data to explore miRNA functions. We also constructed modules to identify metal-associated miRNA networks. Results: We identified 55 metal-associated miRNAs at false discovery rate-adjusted P