Genetic Regulation of Monocyte MicroRNAs and Their Implication in Musculoskeletal Diseases: A Cross-Ancestry Expression Quantitative Trait Loci and Imputation Study

This study investigated the genetic regulation of microRNA (miRNA) expression in monocytes and its potential role in musculoskeletal diseases. We mapped expression quantitative trait loci (eQTLs) for miRNAs using data from 281 Caucasian (CAU) and 170 African American (AA) individuals, constructed ancestry-specific models to impute miRNA expression from genotype data, and applied these models to test associations with osteoporosis and sarcopenia. Analysis identified 468 and 2653 independent eQTLs for 61 miRNAs in CAU and 25 in AA, respectively, the majority of which were ancestry-specific. Association analyses identified 22 and 26 miRNAs associated with osteoporosis and sarcopenia, respectively, in the CAU population; corresponding findings in the African American population were 26 and 14 miRNAs. Analysis of their target genes revealed 1238 and 741 genes that were nominally associated with osteoporosis and sarcopenia in CAU; with 524 genes associated with osteoporosis and 891 associated with sarcopenia in AA. Functional enrichment analysis indicated that the target genes of the identified miRNAs are involved in disease-relevant biological processes-cell migration and motility in osteoporosis, and immune/cytokine responses in sarcopenia. This work provides insights into the genetic architecture of miRNA expression and implicates monocyte miRNAs in musculoskeletal diseases, underscoring the importance of including diverse ancestral backgrounds in genomic studies.