Analysis Of Environmental Genetic Factors And Mining Of Comorbidity Patterns Of Sleep Disorders In Brain And Manual Workers In Xinjiang

Objective: A cross-sectional study was conducted to investigate the prevalence of sleep problems and related factors among mental and manual workers in Xinjiang.To explore the association of circadian CLOCK gene,BMAL1 gene,CRY1 gene,PER2 gene,NR1D1 gene and RORA gene polymorphisms and expression levels with sleep disorders.To explore the comorbidity pattern of brain/manual workers in Xinjiang and establish a comorbidity network model.Methods: 1)Cluster random sampling method was used to use the Effort-Reward Imbalance scale(ERI),Maslach Burnout InventoryGeneral Survey(MBI-GS),Self-reporting Inventory(SCL-90),Athens Insomnia Scale(AIS),Pittsburgh Sleep Quality Index(PSQI),and musculoskeletal disorders questionnaire.A questionnaire survey was conducted among 1405 mental workers and1438 manual workers in Xinjiang.2)50% of the mental and manual workers with sleep disorders were randomly selected for genetic polymorphism analysis.im LDR genotyping technology was used to detect CLOCK(rs10462028\rs11932595),BMAL1(rs10832018\rs1026071),CRY1(rs1056560\rs2287161),PER2(rs934945\rs2304)672),NR1D1(rs939347\ rs2314339)and RORA(rs3743266\rs10851687)genes and sleep disorders.3)Real-time PCR was used to detect the expression of six circadian clock genes,and the differences in gene expression levels between the sleep disorder group and the healthy control group were compared.4)Association rule analysis was used to mine the data of multimorbidity among brain and manual workers in Xinjiang,and Cytoscape was used to conduct network analysis and establish a multimorbidity network model.Results: 1)6.8%of the brain workers and 12.5% of the manual workers had sleep duration less than 6hours.The risk of sleep duration<7 hours in women was 1.408 than that in men(OR=1.408,95%CI:1.079-1.838).Bachelor’s degree(OR=2.319,95%CI:1.265-4.249),master’s degree or above(OR=2.515,95%CI:1.265-5.002),shift work(OR=4.084,95%CI:2.839-5.874),smoking(OR=1.646,95%CI:1.179-2.299),drinking(OR=2.331,95%CI:1.660-3.272),fat(OR=1.609,95%CI:1.161-2.229)were risk factors for insufficient sleep duration.2)The incidence of insomnia was 51.7% in the mental labor group and47.3% in the physical labor group.Shift(OR=1.347,95%CI:1.076-1.686),drinking(OR=1.378,95%CI:1.124-1.691),dyslipidemia(OR=1.289,95%CI:1.003-1.658),high uric acid hematic disease(OR=1.830,95%CI:1.365-2.454),Helicobacter pylori positive(OR=1.636,95%CI:1.368-1.956),WMSDs(OR=2.265,95%CI:1.885-2.720),occupational stress(OR=1.537,95%CI:1.290-1.831),job burnout(OR=1.900,95%CI:1.587-2.273)and mental disorders(OR=4.343,95%CI:3.648-5.169)were risk factors for insomnia.3)The prevalence of sleep disorders was 24.3% in mental workers and 36.4% in manual workers.Alcohol drinking(OR=1.399,95%CI:1.046-1.869),hyperuricemia(OR=1.681,95%CI:1.139-2.480),Helicobacter pylori positive(OR=1.356,95%CI:1.051-1.748),job burnout(OR=1.578,95%CI:1.226-2.030),mental disorders(OR=1.836,95%CI:1.401-2.406),insomnia(OR=57.078,95%CI:36.843-88.428)and insufficient sleep(OR=5.509,95%CI:4.268-7.112)were the risk factors for sleep disorders.Random forest risk prediction model showed that sleep duration,insomnia and psychological disorders were the top three variables to predict the occurrence of sleep disorders.4)The A allele of CLOCK gene rs10462028 increased the risk of sleep disorders by 34.2%(OR=1.342,95%CI:1.004-1.796).The G allele of CLOCK gene rs11932595 increased the risk of sleep disorders by 52.3%(OR=1.523,95%CI:1.125-2.061).There was no significant difference in the gene frequency of BMAL1 gene rs10832018 locus under the allele model,codominant model,dominant model,recessive model and overdominant model between the case group and the control group(P>0.05).AA genotype of rs1026071 in BMAL1 gene decreased the risk of sleep disorders by 27.1%(OR=0.729,95%CI:0.0543-0.980).There was no significant difference in the gene frequency of rs1056560 locus of CRY1 gene between the case group and the control group under the allele model,codominant model,dominant model,recessive model and overdominant model(P>0.05).The C allele of CRY1 rs2287161 increased the risk of sleep disorders by 39.2%(OR=1.392,95%CI: 1.090-1.776).The PER2 gene rs934945 T allele had an increased risk of sleep disorders by 29.5%(OR=1.295,95%CI:1.044-1.606),and the TT genotype had a 2.043 times higher risk of sleep disorders than the CC genotype(95%CI:1.129-3.696).The risk of sleep disorders with the C allele of rs2304672 in PER2 gene decreased by 28.2%(OR=0.718,95%CI:0.521-0.990),and the risk of sleep disorders with the GC genotype decreased by 36.2% compared with the GG genotype(OR=0.638,95%CI:0.445-0.917).The risk of sleep disorders in NR1D1 gene rs939347 GA genotype was 1.545 times that of GG genotype(95%CI:1.127-2.116),and the risk of sleep disorders in NR1D1 gene rs939347 GA+AA genotype increased by 47.3%(OR=1.473,95%CI:1.094-1.982);There was no significant difference in the gene frequency of NR1D1 gene rs2314339 locus under the allele model,codominant model,dominant model,recessive model and overdominant model between the case group and the control group(P>0.05).There were no significant differences in the gene frequencies of RORA gene rs3743266 and rs10851687 loci under the allele model,codominant model,dominant model,recessive model,and overdominant model between the case group and the control group(P>0.05).5)The results of SHEsis software showed that the CLOCK gene A-G haplotype and CRY1 gene C-C haplotype may increase the risk of sleep disorders;CLOCK gene G-A haplotype,CRY1 gene G-A haplotype,PER2 gene C-G haplotype,NR1D1 gene T-G haplotype may reduce the risk of sleep disorders.6)Gene-gene and gene-environment interactions on sleep disorders were constructed by GMDR,and the results showed that there were interactions among CLOCK rs10462028,BMAL1 rs1026071,NR1D1rs939347.There was an interaction between CLOCK rs10462028* insomnia and PER2rs2304672*sleep time*insomnia.7)The expression levels of CLOCK,BMAL1,CRY1,PER2 and RORA genes in the sleep disorder group were lower than those in the healthy control group;The expression levels of BMAL1,CRY1,PER2,CLOCK and RORA genes were negatively correlated with PSQI score and AIS score,and the expression levels of BMAL1,CLOCK and RORA genes were positively correlated with sleep time.8)The prevalence of multimormality was 79.5% in mental workers and 72.3% in manual workers.Compared with the mental workers,the manual workers had a 23.4% reduction in the risk of multimorbidity.A total of 12 comorbidity patterns were identified,including 7 ternary comorbidity patterns,4 quaternary comorbidity patterns,and 1five-triad comorbidity pattern(sleep disorders,musculoskeletal disorders,mental disorders,Helicobacter pylori infection,and insomnia).Conclusion: 1)The incidence of insufficient sleep among mental workers was lower than that among manual workers.2)The incidence of insomnia in mental workers is higher than that in manual workers.3)The incidence of sleep disorders in mental workers is lower than that in manual workers.Sleep duration,insomnia,and psychological disorders are important factors affecting sleep disorders.4)CLOCK rs10462028,rs11932595,BMAL1 rs1026071,CRY1rs228716,PER2 rs934945,and NR1D1 rs939347 were susceptible genes for sleep disorders.5)Lower expression of CLOCK,BMAL1,CRY1,PER2 and RORA genes in sleep disorder group.6)There was a high degree of comorbidity among sleep disorders,musculoskeletal disorders,psychological disorders,Hp infection and insomnia.