Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways

摘要: Chronic widespread musculoskeletal pain (CWP) and frailty are prevalent conditions in older people. We have shown previously that interindividual variation CWP is genetically determined. also reported an association of caused by shared genetic common environmental factors. The aim this study was to use omic approaches identify molecular factors underlying the heritability its correlation with CWP. Frailty quantified through Rockwood Index (FI) as a proportion deficits from 33 binary health deficit questions 3626 female twins. Common assessed using screening questionnaire. OMICS analysis included 305 metabolites whole-genome (>2.5 × 10 SNPs) epigenome (∼1 MeDIP-seq regions) assessments performed on fasting blood samples. Using family-based statistical analyses, including path analysis, we examined how FI scores were related CWP, taking into account known risk such fat mass smoking. significantly correlated 51 after correction for multiple testing, 20 having P-values between 2.1 4.0 10. Three (uridine, C-glycosyl tryptophan, N-acetyl glycine) statistically independent thought exert direct effect FI. Epiandrosterone sulphate, be highly inversely associated found indirect influence Bioinformatics genome-wide EWAS showed covariation genomic regions involved neurological pathways. Neurological pathway involvement accounts aging