PheSeq, a Bayesian deep learning model to enhance and interpret the gene-disease association studies.

Despite the abundance of genotype-phenotype association studies, the resulting association outcomes often lack robustness and interpretations. To address these challenges, we introduce PheSeq, a Bayesian deep learning model that enhances and interprets association studies through the integration and perception of phenotype descriptions. By implementing the PheSeq model in three case studies on Alzheimer's disease, breast cancer, and lung cancer, we identify 1024 priority genes for Alzheimer's disease and 818 and 566 genes for breast cancer and lung cancer, respectively. Benefiting from data fusion, these findings represent moderate positive rates, high recall rates, and interpretation in gene-disease association studies.

Relationship between exposure to metalworking fluids and nonalcoholic fatty liver disease.

OBJECTIVE: The relationship between metalworking fluids (MWFs) and nonalcoholic fatty liver disease (NAFLD) has not been previously explored. We aim to investigate the relationship between occupational exposure to MWFs and the prevalence of NAFLD and to determine the cumulative exposure threshold per day. METHODS: In 2020, 2079 employees were selected randomly from one computer numerical control machining factory in Wuxi for a questionnaire survey, and occupational health examinations were conducted at the affiliated branch of Wuxi Eighth People's Hospital. MWF samples were collected within the factory using the National Institute for Occupational Safety and Health (NIOSH) 5524 method. NAFLD was defined as having a hepatic steatosis index (HSI) ≥ 36 without significant alcohol consumption. The relationship between NAFLD and MWFs was analyzed using logistic regression, and the daily exposure threshold was calculated using R software. RESULTS: MWF exposure was found to be a risk factor for NAFLD in exposed workers compared to the non-exposed group. The OR for NAFLD in workers exposed to MWFs compared to controls was 1.42 (95% CI: 1.04-1.95). An increased risk of NAFLD was shown to be associated with an increasing dose. The daily exposure dose threshold to MWFs was found to be 6.54 mg/m3 (OR = 2.09, 95% CI: 1.24-3.52). CONCLUSION: An association between occupational exposure to MWFs and NAFLD was found. As the concentration of exposure rose, the prevalence of NAFLD was also escalated.

Association between occupational noise and obesity: a retrospective cohort study in China.

OBJECTIVES: To determine the relationship between occupational noise, and obesity and body mass index (BMI) changes. METHODS: Baseline data were collected from participants (n = 1264) who were followed for 6 years in a retrospective study. The noise exposure level (LAeq,8h) was determined by equivalent continuous weighted sound pressure levels using the fixed-point surveillance method for noise monitoring. The cumulative noise exposure (CNE) level was determined using the equal energy formula, which is based on exposure history and level. RESULTS: The incidence of obesity at low (RR = 2.364, 95% CI 1.123-4.739]), medium (RR = 3.921, 95% CI 1.946-7.347]), high (RR = 5.242, 95% CI 2.642-9.208]), and severe noise levels (RR = 9.322, 95% CI 5.341-14.428]) was higher risk than the LAeq,8h control level. The risk of obesity among participants exposed to low (RR = 2.957, 95% CI 1.441-6.068]) and high cumulative noise levels (RR = 7.226, 95% CI 3.623-14.415]) was greater than the CNE control level. For every 1 dB(A) increase in LAeq,8h, the BMI increased by 0.063 kg/m2 (95% CI 0.055-0.071], SE = 0.004). For every 1 dB(A) increase in the CNE, the BMI increased by 0.102 kg/m2 (95% CI 0.090-0.113], SE = 0.006). CONCLUSIONS: Occupational noise is related to the incidence of obesity. The occupational noise level and occupational noise cumulative level were shown to be positively correlated with an increase in BMI.

A cohort study on the association between changing occupational stress, hair cortisol concentration, and hypertension.

OBJECTIVE: To explore the relationship between changing occupational stress levels, hair cortisol concentration (HCC), and hypertension. METHODS: Baseline blood pressure of 2520 workers was measured in 2015. The Occupational Stress Inventory-Revised Edition (OSI-R) was used to assess changes in occupational stress. Occupational stress and blood pressure were followed up annually from January 2016 to December 2017. The final cohort numbered 1784 workers. The mean age of the cohort was 37.77±7.53 years and the percentage male was 46.52%. At baseline, 423 eligible subjects were randomly selected for hair sample collection to determine cortisol levels. RESULTS: Increased occupational stress was a risk factor for hypertension [risk ratio (RR) = 4.200, 95% confidence interval (CI): 1.734-10.172]. The HCC of workers with elevated occupational stress was higher than that of workers with constant occupational stress [(ORQ score ≥70: geometric mean±geometric standard deviation = 5.25±3.59 ng/g hair; 60-90: 5.02±4.00; 40-59: 3.45±3.41; <40: 2.73±3.40) x2 = 5.261]. High HCC increased the risk of hypertension (RR = 5.270, 95% CI: 2.375-11.692) and high HCC was associated with higher rates of elevated diastolic and systolic blood pressure. The mediating effect of HCC was 0.51[(95% CI: 0.23-0.79, odds ratio(OR) = 1.67] and accounted for 36.83% of the total effect. CONCLUSIONS: Increased occupational stress could lead to an increase in hypertension incidence. High HCC could increase the risk of hypertension. HCC acts as a mediator between occupational stress and hypertension.

Shift patterns, physical exercise, and Type 2 diabetes mellitus (T2DM): a prospective cohort study in China.

To examine the relationships between different shift patterns and Type 2 diabetes mellitus (T2DM) risk, and determine whether physical exercise reduced the incidence of T2DM in shift workers in the oil industry. Baseline data were collected from participants in May 2013 who were then followed for 4 years in a prospective cohort study. The cohort initially consisted of 3,002 workers and ultimately included 2,827 people. Baseline and follow-up questionnaires were sent to participants every 2 years (in May 2015 and May 2017) to update medical and lifestyle information during the follow-up period. The risk of T2DM among two shift workers [relative risk (RR) = 3.442, 95% CI: 1.904-6.799)], three shift workers (RR = 2.534, 95% CI: 1.484-4.571), and four shift workers (RR = 4.230, 95% CI: 2.680-7.518) was higher than that among day workers. An increasing trend was observed with respect to T2DM risk, with the lowest risk in three shift workers, moderate risk in two shift workers, and highest risk in four shift workers. In the interactive analysis between shift work and physical exercise, taking part in mild physical exercise increased the risk of T2DM for workers. Four shift workers who took part in mild physical exercise had an increased risk of T2DM. The relative excess risk due to interaction (RERI) was 33.769 (0.398-67.140). The attributable proportion due to interaction [API (%)] was 0.704 (0.529-0.880). The synergy index (SI) was 3.563 (1.900-6.683). Shift work is significantly correlated with increased incidence of T2DM. Risk of T2DM is lowest risk in three shift workers, moderate in two shift workers, and highest in four shift workers. Shift workers who participated in moderate and severe physical exercise had reduced risk of developing T2DM.

This study investigated the role of different shift patterns and physical exercise on type 2 diabetes mellitus (T2DM) risk factors of shift workers. We hypothesized that shift patterns would be correlated with the incidence of type 2 diabetes and that physical exercise would reduce the risk of type 2 diabetes. We studied 2,827 workers using a cohort study design following for 4 years. The study sample consisted of 1,249 fixed-day-shift workers, 650 three-shift workers, 297 two-shift workers, and 631 four-shift workers. We found that compared with fixed day shift workers, alternating shift workers were at an increased risk for developing T2DM. And moderate and severe physical exercise reduced the risk of T2DM in shift workers. We concluded that physical exercise is associated with decreased type 2 diabetes risk in shift workers, particularly when physical exercise is moderate and severe. The findings of the current study may assist enterprise management departments in developing diabetes interventions among shift workers.

The relationships of shift work, hair cortisol concentration and dyslipidaemia: a cohort study in China.

BACKGROUND: Currently, cardiovascular disease is the leading cause of death, and dyslipidaemia is an independent and modifiable major risk factor. Previous studies on shift work with dyslipidaemia and hair cortisol concentration (HCC) have yielded conflicting results. The aim of this study was to clarify the association between shift work, dyslipidaemia, and HCC. We further explored the mediating effect of HCC. METHODS: In this cohort study, baseline data were collected from participants in May 2013. The cohort included 2170 participants- 1348 shift workers and 822 non-shift workers- who were followed up for 6 years with four questionnaire surveys from July 2014, October 2015, and May to December 2019. Hair samples were collected from 340 participants during the baseline period for HCC testing with an automated radioimmunoassay. Dyslipidaemia was defined using the National Cholesterol Education Program Adult Treatment Panel III diagnostic criteria. RESULTS: Shift workers had a higher risk of dyslipidaemia than workers on the fixed day shift (two-shift RR = 1.408, 95% CI: 1.102-1.798; three-shift RR = 1.478, 95% CI: 1.134-1.926; four-shift RR = 1.589, 95% CI: 1.253-2.015). Additionally, shift workers had higher HCC levels than fixed day shift workers, with geometric mean concentration (GMC) ± geometric standard difference (GSD) = 2.625 ± 2.012 ng/g, two-shift GMC ± GSD = 3.487 ± 1.930 ng/g, three-shift GMC ± GSD = 2.994 ± 1.813 ng/g, and four-shift GMC ± GSD = 3.143 ± 1.720 ng/g. High HCC was associated with a high incidence of dyslipidaemia. After controlling for confounding factors, this study showed that HCC played a role in mediating dyslipidaemia in shift workers and accounted for 16.24% of the effect. CONCLUSIONS: Shift work was linked to increased risk of dyslipidaemia compared with fixed day shift work. Higher HCC was associated with a higher prevalence of dyslipidaemia. HCC had a significant mediating effect on dyslipidaemia in shift workers.

Association between sleep disorders and shift work: a prospective cohort study in the Chinese petroleum industry.

Objective. This study aimed to understand the prevalence of sleep disorders among shift workers and analyze the relationship between sleep disorders and shift work. Methods. Baseline data were collected from subjects who were then followed for 2 years in a prospective cohort study. The cohort ultimately included 2453 people starting in May 2013, and follow-up with questionnaires was performed in July 2014 and October 2015. Sleep disorders were assessed with the Pittsburgh sleep quality index. Results. The risk of sleep disorders among two-shift workers (relative risk [RR] = 1.318, 95% confidence interval [CI] [1.025, 1.695]), three-shift workers (RR = 1.326, 95% CI [1.048, 1.679]) and four-shift workers (RR = 1.334, 95% CI [1.062, 1.675]) was higher than that among non-shift workers, and an increasing trend was observed in sleep disorders as the number of shifts increased. Conclusions. Shift workers have a higher incidence of sleep disorders than non-shift workers. An increasing linear trend was observed between the number of shifts and sleep disorders. In the petroleum industry, it is necessary to decrease the frequency of shifts to reduce the incidence of sleep disorders among shift workers.

Relationships among N,N-dimethylformamide exposure, CYP2E1 and TM6SF2 genes, and non-alcoholic fatty liver disease.

OBJECTIVE: This study aimed to examine the relationships among N, N-dimethylformamide (DMF) exposure, cytochrome P4502E1 (CYP2E1) single nucleotide polymorphisms (SNPs) (rs2031920, rs3813867, rs6413432), transmembrane 6 superfamily member 2 (TM6SF2) SNP rs58542926 and non-alcoholic fatty liver disease (NAFLD). METHODS: Baseline data were collected from participants who were then followed for 5 years in a prospective cohort study. The cohort initially consisted of 802 workers and ultimately included 660 people, all of whom underwent annual occupational health examinations from 2010 to 2015. RESULTS: The above-threshold group (≥7.3 mg/m³ adjusted relative risk (RR)= 3.620, 95%CI 2.072-6.325) was significantly more likely to develop NAFLD than the below-threshold group (<7.3 mg/m³). The TM6SF2 SNP rs58542926 CT (adjusted RR=3.921, 95% CI 2.329-6.600, P = 0.000) and CT+TT (adjusted RR=4.385, 95% CI 2.639-7.287, P = 0.000) genotypes were risk factors for NAFLD, as compared with the TM6SF2 rs58542926 CC genotype. Each dose group (below-threshold group and above-threshold group) interacting with the genotype of TM6SF2 SNP rs58542926 had an adjusted RR from 7.764 (95% CI 3.272-18.420, P = 0.000) to 24.022 (95% CI 8.971-64.328, P = 0.000). The T allele of rs58542926 in the TM6SF2 gene may be a risk factor for susceptibility to DMF-induced NAFLD. CONCLUSION: Polymorphisms of TM6SF2 SNP rs58542926 may play an important role in susceptibility to NAFLD after exposure to DMF.

A novel regQTL-SNP and the risk of lung cancer: a multi-dimensional study.

RegQTL, a novel concept, indicates that different genotypes of some SNPs have differential effects on the expression patterns of miRNAs and their target mRNAs. We aimed to identify the association between regQTL-SNPs and lung cancer risk and to explore the underlying mechanisms. The two-stage case-control study included the first stage in a Chinese population (626 lung cancer cases and 667 healthy controls) and the second stage in a European population (18,082 lung cancer cases and 13,780 healthy controls). Functional annotations were conducted based on the GTEx and the TCGA databases. Functional experiments were performed to explore the underlying biological mechanisms in vitro and vivo. After strict screening, five candidate regQTL-SNPs (rs7110737, rs273957, rs6593210, rs3768617, and rs6836432) were selected. Among them, the variant T allele of rs3768617 in LAMC1 was found to significantly increase the risk of lung cancer (first stage: P = 0.044; second stage: P = 0.007). The eQTL analysis showed that LAMC1 expression level was significantly higher in subjects with the variant T allele of rs3768617 (P = 1.10 × 10-14). In TCGA paired database, the regQTL annotation indicated the different expression patterns between LAMC1 and miRNA-548b-3p for the distinct genotypes of rs3768617. Additionally, LAMC1 knockdown significantly inhibited malignant phenotypes in lung cancer cell lines and suppressed tumor growth. A novel regQTL-SNP, rs3768617, might affect lung cancer risk by modulating the expression patterns of miRNA-548b-3p and LAMC1. RegQTL-SNPs could provide a new perspective for evaluating the regulatory function of SNPs in lung cancer development.

The influence of changes in work stressors and coping resources on sleep disturbances: evidence from the OHSPIW cohort study.

STUDY OBJECTIVES: We investigated whether changes in psychosocial work conditions affect the risk of sleep disturbances. METHODS: Data pertaining to 2738 males and 1431 females were obtained from the Occupational Health Study of Petroleum Industry Workers (OHSPIW), a prospective cohort study of Chinese petroleum industry workers. The subjects were assessed with regard to work-related stressors, coping resources, and sleep disturbances at baseline (2012) and follow-up (2018). The variations in work stressors and coping resources, which were assessed using the Occupation Stress Inventory-Reviewed (OSI-R), were calculated. Sleep disturbances were evaluated with the self-reported Pittsburgh Sleep Quality Index (PSQI). RESULTS: Increased work stressors (OR = 1.57, 95% CI = 1.24-1.99) and decreased coping resources (OR = 2.03, 95% CI = 1.48-2.78) were correlated with the likelihood of sleep disturbances in male and female workers. The primary risk factors included high role overload, increased responsibility, enhanced physical environment stressors, reduced self-care, and reduced rational coping. A reduction in work stressors was a protective factor against sleep disturbances in females only (OR = 0.63, 95% CI = 0.45-0.88). Coping resources had a modifying effect on the relationship between increased work stressors and sleep disturbances, with increased coping resources being associated with a lower odds of increased works stressors on sleep disturbances (OR = 1.29, 95% CI = 1.01-1.66) than decreased coping resources (OR = 3.60, 95% CI = 1.10-11.81). CONCLUSIONS: Changes in work stressors and coping resources have a significant influence on the risk of sleep disturbances. Our findings highlight important precautionary strategies to abate adverse psychosocial working environments and to strengthen coping resources to prevent work-related sleep disturbances.

Integrating RNA-Seq With GWAS Reveals a Novel SNP in Immune-Related HLA-DQB1 Gene Associated With Occupational Pulmonary Fibrosis Risk: A Multi-Stage Study.

Objective: To evaluate the association between single-nucleotide polymorphisms (SNPs) in RNA-seq identified mRNAs and silicosis susceptibility. Methods: A comprehensive RNA-seq was performed to screen for differently expressed mRNAs in the peripheral blood lymphocytes of eight subjects exposed to silica dust (four silicosis cases and four healthy controls). Following this, the SNPs located on the shortlisted mRNAs, which may affect silicosis susceptibility, were screened through silicosis-related genome-wide association studies (GWAS) (155 silicosis cases and 141 healthy controls), whereas functional expression quantitative trait locus (eQTL)-SNPs were identified using the GTEx database. Finally, the association between functional eQTL-SNPs and silicosis susceptibility (194 silicosis cases and 235 healthy controls) was validated. Results: A total of 70 differentially expressed mRNAs (fold change > 2 or fold change < 0.5, P < 0.05) was obtained using RNA-seq. Furthermore, 476 SNPs located on the shortlisted mRNAs, which may affect silicosis susceptibility (P < 0.05) were obtained using GWAS, whereas subsequent six functional eQTL-SNPs were identified. The mutant A allele of rs9273410 in HLA-DQB1 indicated a potential increase in silicosis susceptibility in the validation stage (additive model: odds ratio (OR)= 1.31, 95% confidence interval (CI) = 0.99-1.74, P = 0.061), whereas the combination of GWAS and the validation results indicated that the mutant A allele of rs9273410 was associated with increased silicosis susceptibility (additive model: OR = 1.35, 95% CI =1.09-1.68, P = 0.006). Conclusion: The mutant A allele of rs9273410 was associated with increased silicosis susceptibility by modulating the expression of HLA-DQB1.

Dopamine Receptor D2 Gene (DRD2) Polymorphisms, Job Stress, and Their Interaction on Sleep Dysfunction.

Recent studies have shown that incessant job stress could eventually result in sleep dysfunction (SD), and most importantly, the essential role dopamine receptor D2 (DRD2) gene polymorphisms play in the psychopathological mechanism of SD. The Effort-Reward Imbalance scale and the Pittsburgh Sleep Quality Index were both used to access SD and job stress (JS). A significant negative correlation was observed between the sDA levels and SD subscale scores (sleep efficiency, daytime dysfunction). The findings revealed that high levels of JS were linked to a higher SD score (OR = 2.13, 95% CI: 1.46-3.12). Likewise, the homozygous A1A1 genotype of DRD2 rs1800497 was more likely to be associated with SD (OR = 2.90, 95% CI: 1.75-4.82). Compared to participants with low JS and heterozygous A1A2/A2A2 genotype, those with both high JS and homozygous A1A1 genotype had a higher SD score (OR = 5.40, 95% CI: 2.89-10.11). The A1 allele of the DRD2 rs1800497 polymorphism also enhances the likelihood of SD when undergoing JS. Besides, subjects with low JS and the homozygous A1A1 genotype also showed an increased possibility for sleep dysfunction (OR = 2.05, 95% CI: 1.03-4.11). Our results suggest that the DA system may interrelate with JS to affect sleep.

Relationships among shift work, hair cortisol concentration and sleep disorders: a cross-sectional study in China.

OBJECTIVE: The present study was designed to demonstrate the relationships among shift work, hair cortisol concentration (HCC) and sleep disorders. DESIGN: A cross-sectional study. SETTING: Three petroleum administrations in Karamay city of Xinjiang, China. PARTICIPANTS: 435 individuals including 164 males and 271 females participated in the research. OUTCOME MEASURES: Information on shift work was collected by a self-administered questionnaire. HCC was determined using an automatic radioimmunoassay instrument. Sleep quality was measured on the Pittsburgh Sleep Quality Index scale. RESULTS: Shiftwork was associated with an increased prevalence of sleep disorders compared with the fixed day shift (two shifts: OR 3.11, 95% CI 1.57 to 6.19; three shifts: OR 2.87, 95% CI 1.38 to 5.98; four shifts: OR 2.22, 95% CI 1.17 to 4.18; others: OR 3.88, 95% CI= 1.36 to 11.08). Workers with different shift patterns had higher HCC levels than day workers ((fixed day shift: geometric mean±geometric SD=2.33±1.65; two shifts: 3.76±1.47; three shifts: 3.15±1.64; four shifts: 3.81±1.55; others: 3.60±1.33) ng/g hair, η2=0.174) and high HCC was associated with the higher prevalence of sleep disorders (OR 4.46, 95% CI 2.70 to 7.35). The mediating effect of HCC on the relationship between shift work and sleep disorders was 0.25 (95% CI 0.09 to 0.41). CONCLUSION: We found that, when compared with the fixed day shift, shiftwork was associated with both the higher HCC, and also with an increased risk of sleep disorders. High HCC was associated with the occurrence of sleep disorders. In addition, HCC had mediating effect in shift work and sleep disorders. Thus, HCC can be considered as an early marker of shiftwork circadian disruption to early detection and management of sleep disorders.

Association between CYP2E1 and GOT2 gene polymorphisms and susceptibility and low-dose N,N-dimethylformamide occupational exposure-induced liver injury.

OBJECTIVE: To investigate the effects of the interactions between the CYP2E1 and GOT2 gene polymorphisms and N,N-dimethylformamide (DMF) on liver injury. METHODS: A total of 672 DMF-exposed workers were randomly selected from two synthetic leather enterprises in Suzhou, China, for follow-up in a cohort study. Information on exposure to DMF in the air was collected through a fixed-point air sampler in the worker's breathing zone. The subjects were assessed every year during the period of 2010-2015, they underwent occupational health examinations. Alanine aminotransferase and aspartate aminotransferase levels were measured. Peripheral blood was collected and DNA was extracted. The genotypes rs2031920, rs3813867 and rs6413432 of the CYP2E1 gene and rs7204324 of the GOT2 gene were detected by PCR, and analyzed using the Chi-square test and logistic regression analysis. RESULTS: Workers exposed to a high cumulative dose of DMF were significantly more likely than low-exposed workers to develop liver injury. No association was observed between rs2031920, rs3813867 and rs6413432 of the CYP2E1 gene and DMF-induced liver damage. However, the A allele of rs7204324 on the GOT2 gene may be a risk factor for susceptibility to DMF-induced liver injury. CONCLUSION: Polymorphisms of rs7204324 on GOT2 may play an important role in susceptibility to liver injury following exposure to DMF.

Relationship between N,N-dimethylformamide exposure, PNPLA3, GCKR, COL13A1 and TM6SF2 genes, and liver injury.

BACKGROUND: Current researches show that N,N-dimethylformamide (DMF) exposure is associated with liver injury, but it is debatable whether PNPLA3, GCKR, COL13A1 and TM6SF2 gene polymorphisms are associated with liver injury. Our objective was to examine the relationship among DMF exposure, PNPLA3 rs738409, GCKR rs780094, COL13A1 rs1227756, TM6SF2 rs58542926 and liver injury. METHODS: The cohort consisted of 461 workers exposed above the DMF threshold limit value (TLV) and 211 exposed below the DMF TLV in China, who were followed for 5 years. The relationship between the measured dose of DMF and the relative risk (RR) of liver injury was also investigated by Poisson analysis. Logistic regression models were used to examine the association between measured dose of DMF, gene locus, and RR for liver injury. All workers had a annual physical examinations were conducted at certified physical examination centers in Taicang CDC, including liver serum transaminase assessment and abdominal ultrasound. Genomic DNA was extracted from peripheral blood leukocytes using a genomic DNA extraction kit. RESULTS: The incidence of liver injury in the above DMF TLV group was significantly higher than in the below DMF TLV group. GCKR rs780094 was associated with liver injury. The interaction among the GCKR rs780094, DMF exposure and liver injury showed no significant association. CONCLUSIONS: Our data indicated that in DMF exposure, GCKR rs780094 may contribute to the risk of liver injury. Our results suggest that GCKR rs780094 is a useful genetic marker to help identify liver injury.

Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

OBJECTIVES: In a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported. METHODS: We systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases. RESULTS: We found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls. CONCLUSIONS: The rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility.

A Novel Variant of Desmoplakin Is Potentially Associated with Silicosis Risk.

Two genome-wide association studies and one sequencing study have coincidently reported significant associations of single nucleotide polymorphisms (SNPs) in the desmoplakin (DSP) gene with the risk of pulmonary fibrosis (mainly idiopathic pulmonary fibrosis). However, these findings have not been well generalized to occupational pulmonary fibrosis (e.g., silica-related silicosis). We systematically genotyped 8 potentially functional SNPs and the previously reported rs2076295 and rs2744371 in DSP gene region and evaluated the associations between these 10 SNPs and silicosis risk in a case-control study that included 177 silicosis cases and 204 controls with similar numbers of silica dust exposure years as the cases from a Chinese population. Genotyping was performed using the improved multiligase detection reaction multiplex SNP genotyping system. The variant A allele of rs2076304 exhibited significant association with the risk of silicosis (odds ratio = 1.53, 95% confidence interval = 1.03-2.29, p = 0.036). Moreover, significant association was observed between different genotypes of rs2076304 and DSP expression (p = 1.1 × 10-7) in 383 normal lung tissues. Further functional annotation indicated that the rs2076304 might influence the binding of RHOXF1. The rs2076304 in DSP gene is associated with a significantly increased risk of silicosis in a Han Chinese population. Further studies are warranted to validate and extend our findings, especially the biological mechanisms of rs2076304 in silicosis susceptibility.

[Prospective cohort study on the occupational stress and mental disorder among the oilfield workers in Xinjiang Autonomous Region in 2013-2015].

OBJECTIVE: To explore the relationship between occupational stress and psychological disorder among oilfield workers. METHODS: In 2013, 1485 psychological normal oilfield workers using the stratified cluster sampling in Xinjiang Autonomous Region were investigated, and the follow-up was conducted in 2015. Occupational stress and mental health status were assessed by questionnaire for the occupation stress and self-rating symptom. RESULTS: The people with mental disorder was 556, the incidence rate was40. 29%. The level of occupational stress level low-high group( RR = 2. 689, 95% CI1. 342-5. 391) and middle-high group( RR = 2. 878, 95% CI 1. 205-6. 875) of mental disorder were higher than the low-low group, the level of Personal Strain Questionnaire low-middle group( RR = 2. 500, 95% CI 1. 700-3. 763) and low-high group( RR =3. 907, 95% CI 1. 955-7. 651) and middle-middle group( RR = 2. 141, 95% CI 1. 016-4. 512) of mental disorder were higher than low-low group. Without drinking( RR =0. 779, 95% CI = 0. 622-0. 976) was protective factor for mental disorders. CONCLUSION: Occupational stress and drinking are the risk factors of mental disorder, it is more practical to multiple measurement of the psychological disorder of occupational stress exposure than single one.

Relationship between Job Stress and 5-HT2A Receptor Polymorphisms on Self-Reported Sleep Quality in Physicians in Urumqi (Xinjiang, China): A Cross-Sectional Study.

The serotonin receptor (5-HTR) plays a key role in sleep quality regulation. Job-related stress is an important factor that influences sleep quality. However, few reports on the interaction between 5-HTR2A polymorphisms and job stress, and how they may impact upon sleep quality are available. Therefore this study investigated the effects of job stress, 5-HTR2A polymorphisms, and their interaction on sleep quality, in physicians. Using a two-stage stratified sampling method, 918 participants were initially invited to participate in the study. After screening for study inclusion and exclusion criteria, 504 subjects were eventually included in the study. Job stress and sleep quality were assessed using the Job Stress Survey (JSS) and Pittsburgh Sleep Quality Index (PSQI), respectively. The 5-HTR2A receptor gene polymorphisms T102C and -1438G/A of were determined using polymerase chain reaction-restriction fragment length polymorphism. Job stress was significantly associated with sleep quality. High levels of job stress were linked to a higher risk of poor sleep quality compared to low or moderate levels [odds ratio (OR) = 2.909, 95% confidence interval (CI): 1.697⁻4.986]. High levels of stress may reduce subjects’ sleep quality, leading to an increase the likelihood of sleep disturbances and subsequent daytime dysfunction. The 5-HTR2A receptor gene polymorphism T102C was not significantly associated with sleep quality in this study, however, the -1438G/A polymorphism was significantly associated with sleep quality. The GG genotype of the -1438G/A polymorphism was linked to poorer sleep quality. When compared with subjects with low job-related stress levels×AG/AA genotype (OR = 2.106, 95% CI: 1.278⁻3.471), physicians with high job-related stress levels×GG genotype had a higher risk of experiencing poor sleep quality (OR = 13.400, 95% CI: 3.143⁻57.137). The findings of our study indicate that job stress and 5-HTR2A receptor gene polymorphisms are associated with sleep quality in physicians. Subjects with high job stress level or/and the -1438G/A GG genotype were more likely to report poor sleep quality, and furthermore, their combination effect on sleep quality was higher than their independent effects, so it may be suggested that job-related stress and genes have a cumulative effect on sleep quality; that is, stress can increase the risk of poor sleep quality, but this effect is worse in a group of people with specific gene polymorphisms.