Study Of The Association Between Sleep And Indicators Of Chronic Inflammation

Background:With the development of modern society and the accelerated pace of people’s lives,the proportion of individuals with sleep problems in the population is increasing in the whole population,and sleep problems have become a major public health problem.Inflammatory mediators,as important molecules involved in the inflammatory response and immune regulation of the body,have been widely studied for their relevance to various diseases and have been shown to serve as biomarkers for many inflammation-related diseases.Currently,the relationship between sleep and systemic chronic inflammation is not well understood,and the association between multiple sleep phenotypes and multiple inflammatory indicators has been rarely reported.In this study,we propose to identify the relationship between sleep and inflammatory indicators using a series of analyses based on a large population database to provide new insights into the genetic explanation of sleep effects on systemic chronic inflammation.Purpose:The aim of this study was to assess whether there is a correlation and causal association between sleep phenotype and inflammatory marker levels and their potential association mechanisms,including shared genetic factors,pleiotropic genes and their functions.Materials and methods:This study was first based on the individual dataset of the UKB cohort,which included a total of 343,082 study subjects after uniform screening criteria for data from more than 500,000 people.Spearman correlation analysis and multivariate linear correlation analysis were used to evaluate the association between five sleep phenotypes(sleep duration,insomnia,daytime napping,daytime sleepiness,and snoring)and nine inflammatory marker levels(ALB,ALP,CRP,VITD,RDW,WBC,TG,APOA1,and HbA1c),respectively.Then,based on the publicly available GWAS pooled dataset from UKB,two-by-two LDSC analysis was performed for different sleep phenotypes and inflammatory indicators to determine whether there was a genetic correlation;PLACO analysis was performed to identify pleiotropic loci and genes associated with sleep and inflammatory indicators based on the genetic correlation identified by LDSC;and tools such as FUMA were used to perform the identified pleiotropic genes Enrichment analysis and functional annotation of the identified pleiotropic genes were performed using tools such as FUMA to explore the relevant biological pathways and thus elucidate the possible mechanisms underlying the association.In addition,MR analysis of the five selected sleep phenotypes and nine inflammatory indicators was performed to identify the causal associations between them.Results:Spearman correlation analysis showed that all five sleep indicators correlated with nine chronic inflammatory indicators.Multiple linear regression analysis showed that the correlations between two pairs of phenotypes were statistically significant,except for snoring and ALP,insomnia and WBC,which were not correlated.LDSC analysis revealed genetic correlations between most sleep phenotypes and inflammatory indicators,most of which were positive,with a mean of 0.120,and negative genetic correlations were found between some sleep phenotypes and inflammatory indicators,with a mean of-0.102,suggesting that there may be a common genetic basis between each sleep phenotype and each inflammatory marker,while the negative genetic correlations suggest that there may be opposite mechanisms.Among them,the negative genetic correlations suggest that the two have opposite genetic effect mechanisms.Based on these correlations,PLACO analysis further identified pleiotropic genes,such as the histone cluster family olfactory receptor family,and the biological pathways enriched included mainly olfactory conductance,systemic lupus erythematosus,and histone modification pathways.The results of SVMR analysis supported the causal association between sleep and chronic inflammatory indicators,Multiple MR analysis methods have observed a risk causal effect of daytime nap on HbAlc and TG(OR>1),a protective causal effect on VITD and APOA1(OR<1).Daytime nap has a risk causal effect on HbA1c and ALP(OR>1),and a protective causal effect on VITD and APOA1(OR<1).Snoring has a risk causal effect on TG and CRP(OR>1),and a protective causal effect on ALB and VITD(OR>1).Based on the SVMR results,daytime sleepiness,daytime napping,snoring and inflammatory indicators with which causal associations existed were selected for MVMR,and it was found that the causal associations between snoring and inflammatory indicators still significant and in the same direction as the S VMR results.It is suggested that an independent causal effect of snoring on indicators of systemic chronic inflammation.Conclusions:This study identified correlations and causal associations between sleep phenotypes and inflammatory indicators,and discovered pleiotropic genetic factors,pleiotropic genes and their functions shared between the two.The results of this study found that daytime sleepiness,snoring and daytime napping were positively correlated with pro-inflammatory indicators and negatively correlated with anti-inflammatory indicators,confirming the close association between sleep and chronic inflammation,and the results highlight the impact of healthy sleep on the inflammatory state of the body,providing clues and directions for an indepth exploration of the mechanisms of action of sleep affecting systemic chronic inflammation.The findings of this study suggest that improved sleep can help reduce the level of systemic inflammation,thereby reducing the incidence of many chronic and metabolic diseases and improving the quality of life of the population.