Insomnia affects the levels of plasma bilirubin and protein metabolism: an observational study and GWGEIS in UK Biobank cohort

Abstract

Study objectivesWe aim to explore the mechanism of relationship between insomnia and liver metabolism by examining the gene × insomnia interactions. MethodsIndividual level genotypic and phenotypic data were obtained from the UK Biobank cohort. Regression analysis was first conducted to test the association of insomnia with plasma total bilirubin (TBil; n = 186,793), direct bilirubin (DBil; n = 159,854) and total protein (TP; n = 171,574) in UK Biobank cohort. Second, genome-wide gene-environment interaction study (GWGEIS) was conducted by PLINK 2.0, and FUMA platform was used to identify enriched pathway terms. ResultsIn UK Biobank cohort, we found that TP (P < 2.00 × 10−16), DBil (P = 1.72 × 10−3) and TBil (P = 3.38 × 10−5) were significantly associated with insomnia. GWGEIS of both DBil and TBil observed significant G × INSOMNIA effects between insomnia and UDP Glucuronosyltransferase Family 1 (rs6431558, P = 6.26 × 10−11) gene. GWGEIS of TP also detected several significant genes interacting with insomnia, such as KLF15, (rs70940816, P = 6.77 × 10−10) and DOK7, (rs2344205, P = 1.37 × 10−9). Multiple gene ontology (GO) terms were identified for bilirubin, such as GO_URONIC_ACID_METABOLIC_PROCESS (adjusted P = 4.15 × 10−26). ConclusionOur study results suggested negative associations between insomnia and DBil and TBil; and a positive association between insomnia and TP.