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To evaluate the interaction effects of Polycyclic aromatic hydrocarbons (PAHs) exposure and variants in cGAS-STING genes on mitochondrial DNA copy number (mtDNAcn) in workers. The mtDNAcn was determined by real-time quantitative polymerase-chain reaction in 544 PAHs-exposed workers and 238 office workers. The polymorphisms were detected by flight mass spectrometry. The mtDNAcn in PAHs exposure group was significantly lower than non-occupational exposure population (P < 0.00). The cGAS rs610913 CA+AA had significant interaction effects with STING rs11554776 GG+GA (P = 0.035), rs7380824 CC+CT (P = 0.026), and rs78233829 GC+CC (P = 0.034) on mtDNAcn. The generalized linear model results showed that the influencing factors of mtDNAcn include PAHs exposure (P < 0.001) and the interaction of PAHs exposure and cGAS rs 311678 AA+AG (P = 0.047). The influencing factors of mtDNAcn include PAHs exposure and the interaction of PAHs exposure and cGAS rs 311678 AA+AG. [ABSTRACT FROM AUTHOR]

We explored the association between variations in the telomere maintenance genes and change in telomere length (TL) in workers. The TL of peripheral blood leukocytes from 544 coke oven workers and 238 controls were detected using the Real-time PCR method. Variations in four genes were then detected using the PCR based restriction fragment length polymorphism. The effects of environmental and genetic factors on TL were subsequently analyzed through covariance analysis and a generalized linear model.The TL of subjects with GG genotypes were longer than those with AG genotype in the TERT rs2736098 locus amongst the controls (P =.032). The combined effect of COEs exposure and AG+AA genotypes had a significant effect on TL (P <.001). The interaction between the COEs exposure factor and the rs2736098AG+AA genotypes had a significant effect on the TL (P <.05). The TL in coke oven workers is associated with the interactions between TERT rs2736098 AG+AA and COEs exposure. [ABSTRACT FROM AUTHOR]

Coke oven emissions (COEs), confirmed human carcinogens, are mainly composed of polycyclic aromatic hydrocarbons (PAHs). Telomere shortening in blood leukocytes has been associated with COEs, and polymorphisms in metabolic enzymes. However, the relationship between polymorphisms in telomere related genes and telomere shortening in COEs exposed workers has never been evaluated. Therefore, we measured telomere length and mRNA expression levels of telomere-binding proteins (TBPs) by qPCR method in leucocyte from 544 COEs exposed workers and 238 office staffs (referents). Flight mass spectrometry was used to perform the genotyping of selected functional and susceptible SNPs. The results showed that the telomere length in the exposure group 0.75(0.51,1.08) was significantly shorter than that in the control group 1.05(0.76,1.44) (P < 0.001). The mRNA expression levels of TPP1 , TERF1 and TERF2 genes in the exposure group were significantly lower than those in the control group (P < 0.05), the mRNA expression level of POT1 in the exposure group was significantly higher than that in the control group (P < 0.05). We used the wild homozygous genotype as a reference, subjects carrying TERT rs2736109 AA, TERT rs3215401 CC and TERT rs2736100 GT + GG genotypes had significantly longer telomere length in the exposure group (P < 0.05). In conclusion, the workers exposed to COEs had shorter telomere length, which was regulated by the TPP1 , TERF1 , TERF2 and POT1 genes expression levels, and the gene polymorphisms of TERT gene were associated with the telomere length among PAHs-exposure workers. Image 1 • Workers exposed to COEs had shorter RTL, regulated by TPP1 , TERF1 , TERF2 and POT1 genes. • TERT gene polymorphisms were associated with the RTL. [ABSTRACT FROM AUTHOR]

Abstract Omethoate, an organophosphorous pesticide, causes a variety of health effects, especially the damage of chromosome DNA. The aim of the study was to assess the correlation between polymorphisms of encoding miRNA genes and telomere length in omethoate–exposure workers. 180 workers with more than 8 years omethoate–exposure and 115 healthy controls were recruited in the study. Genotyping for the selected single nucleotide polymorphisms loci were performed using the flight mass spectrometry. Real-time fluorescent quantitative polymerase chain reaction(PCR) method was applied to determine the relative telomere length(RTL) in human peripheral blood leukocytes DNA. After adjusting the covariate of affecting RTL, covariance analysis showed that the female was significantly longer than that of the male in control group(P < 0.046). For the miR-145 rs353291 locus, this study showed that RTL of mutation homozygous AG+GG individuals was longer than that of wild homozygous AA in the exposure group (P = 0.039). In the control group, RTL with wild homozygous TT genotype in miR-30a rs2222722 polymorphism locus was longer than that of the mutation homozygous CC genotype (P = 0.038). After multiple linear regression analysis, the independent variables of entering into the model were omethoate–exposure (b = 0.562, P < 0.001), miR-145 rs353291 (AG+GG) (b = 0.205, P = 0.010). The prolongation of relative telomere length in omethoate exposed workers was associated with AG+GG genotypes in rs353291 polymorphism of encoding miR-145 gene. Graphical abstract fx1 Highlights • The encoding miRNA genes and telomere length under omethoate exposure. • Omethoate-exposure and miR-145 genetic polymorphism affect telomere length. • Prolongation of RTL in workers exposed to omethoate with rs353291 AG+GG genotypes. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies have been extensively applied in identifying SNP associated with major psychiatric disorders. However, the SNPs identified by the prevailing univariate approach only explain a small percentage of the genetic variance of traits, and the extensive data have shown the major psychiatric disorders have common biological mechanisms and the overlapping pathophysiological pathways.Methods: We applied the genetic pleiotropy-informed metaCCA method on summary statistics data from the Psychiatric Genomics Consortium Cross-Disorder Group to examine the overlapping genetic relations between the five major psychiatric disorders. Furthermore, to refine all genes, we performed gene-based association analyses for the five disorders respectively using VEGAS2. Gene enrichment analysis was applied to explore the potential functional significance of the identified genes.Results: After metaCCA analysis, 1147 SNPs reached the Bonferroni corrected threshold (p < 1.06 × 10-6) in the univariate SNP-multivariate phenotype analysis, and 246 genes with a significance threshold (p < 3.85 × 10-6) were identified as potentially pleiotropic genes in the multivariate SNP-multivariate phenotype analysis. By screening the results of gene-based p-values, we identified 37 putative pleiotropic genes which achieved significance threshold in metaCCA analyses and were also associated with at least one disorder in the VEGAS2 analyses.Limitations: Alternative approaches and experimental studies may be applied to check whether novel genes could still be identified/substantiated with these methods.Conclusions: The metaCCA method identified novel variants associated with psychiatric disorders by effectively incorporating information from different GWAS datasets. Our analyses may provide insights for some common therapeutic approaches of these five major psychiatric disorders based on the pleiotropic genes and common mechanisms identified. [ABSTRACT FROM AUTHOR]

Omethoate, an organophosphorous pesticide, can cause a variety of health effects, especially the decrease of cholinesterase activity. The aim of this study is to explore the association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed population. Cholinesterase activities in whole blood, red blood cell and plasma were detected using acetylthiocholine and dithio-bis-(nitrobenzoic acid) method; Genetic Genotyping of POT 1 rs1034794, POT 1 rs10250202, TERF 1 rs3863242 and TERT rs2736098 were performed with PCR-RFLP. The cholinesterase activities of whole blood, red blood cells and plasma in exposure group are significantly lower than that of the control group ( P  < 0.001). Multivariate analysis indicates that exposure group ( b  = − 1.016, P  < 0.001), agender ( b  = 0.365, P  < 0.001), drinking ( b  = 0.271, P  = 0.004) and TERF1 rs3863242 ( b  = − 0.368, P  = 0.016) had an impact on cholinesterase activities. The results suggest that individual carrying AG+GG genotypes in TERF 1 gene rs3863242 polymorphism were susceptible to damage in cholinesterase induced by omethoate. [ABSTRACT FROM AUTHOR]

Coke oven emissions (COEs) contain many carcinogenic polycyclic aromatic hydrocarbons (PAHs). Telomere damage is an early biological marker reflecting long-term COEs-exposure. Whereas, whether the genetic variations of telomere-regulated gene TNKS have an effect on the COEs-induced telomere damage is unknown. So we detected the environmental exposure levels, relative telomere length (RTL), and TNKS genetic polymorphisms among 544 COEs-exposure workers and 238 healthy participants. We found that the RTL of the wild homozygous GG genotype in rs1055328 locus was statistically shorter compared with the CG+CC genotype for the healthy participants using covariance analysis(P = 0.008). In the Generalized linear model (GLM) analysis, TNKS rs1055328 GG could accelerate telomere shortening (P = 0.011); and the interaction between TNKS rs1055328 GG and COEs-exposure had an effect on RTL (P = 0.002). In conclusion, this study was the first to discover the role of TNKS rs1055328 locus in COEs-induced telomere damage, and proved that chromosomal damage was a combined consequence of environmental and genetic factors. • Cumulative exposure dose (CED), and 1-OHPYR were significantly negatively correlated with RTL. • TNKS rs1055328 GG could promote telomere damage. • The interaction between TNKS rs1055328 GG and COEs-exposure had an effect on RTL. [ABSTRACT FROM AUTHOR]

Telomeres are located at the end of eukaryotic chromosomes and vulnerable to exogenous chemical compounds. Exposure to coke oven emissions (COEs) leads to a dose-related telomere damage, and such chromosomal damage might trigger the cGAS / STING signaling pathway which plays an important role in immune surveillance. However, the relationship between the genetic variations in the cGAS / STING signaling pathway and telomere damage in the COEs-exposure workers has not been investigated. Therefore, we recruited 544 coke oven workers and 238 healthy control participants, and determined the level of COEs exposure, concentration of urinary 1-hydroxypyrene (1-OHPYR), genetic polymorphisms and telomere length. The results showed that the telomere length significantly decreased from the control-to high-exposure groups as defined by the external exposure level (P < 0.05). The results also indicated that STING rs7447927 CC, cGAS rs34413328 AA, and cGAS rs610913 AA could inhibit telomere shortening in the exposure group (P < 0.05), and cGAS rs34413328, urine 1-OHPYR and cumulative exposure dose (CED) had a significant association with telomere length by generalized linear model. In conclusion, telomere shortening was a combined consequence of short-term exposure, long-term exposure, and genetic variations among the COEs-exposure workers. Image 1 • Urine 1-OHPYR was negatively related to telomere length. • Telomere length was associated with the total cumulative exposure dose. • Rs34413328 AA could slow down telomere shortening in the coke oven workers. [ABSTRACT FROM AUTHOR]

Peripheral blood leukocyte telomere length in omethoate–exposed workers is related to environmental exposure and single nucleotide polymorphisms (SNPs) in genes including p21 , GSTM1, miR-145, etc. However, the roles of SNPs in tankyrase (TNKS) gene in telomere length are still unknown. The aim of this study was to explore the association between SNPs in TNKS gene and telomere length in omethoate–exposed workers. Telomere length in peripheral blood leukocyte DNA from 180 omethoate-exposed workers and 115 healthy controls was measured using Real-time quantitative polymerase chain reaction (PCR). Genotyping of the selected functional and susceptible SNPs was performed by the flight mass spectrometry based on PCR and single-base extension. The analysis of covariance was performed to find effects of SNPs on telomere length. Generalized linear models were used to analyze the environment, gene, and interaction on telomere length. The results showed that telomere length in the CG + CC genotypes in rs1055328 in TNKS gene was significantly longer than that in the wild homozygous GG genotype both in exposure group (P = 0.017) and in control group (P = 0.038) after adjusting the covariates. The variables kept in the generalized linear models included omethoate-exposure (β = 0.580, P = 0.001) and rs1055328 (CG + CC) in TNKS gene (β = 0.339, P = 0.002). The study suggests that the prolongation of telomere length is associated with omethoate-exposure and the CG + CC genotypes in rs1055328 in TNKS gene. • A new method is established for detecting seven SNPs in TNKS gene by MALDI-TOF MS. • Omethoate workers carrying rs1055328 CG + CC genotypes have longer telomere. • Other six SNPs are unrelated to changes in telomere length in omethoate workers. [ABSTRACT FROM AUTHOR]

• The omethoate exposure could increase the level of H 2 O 2. • POT1 rs034794 AA + AT genotype is a risk factor of the increase H 2 O 2 level. • The polymorphisms in POT1 rs10250202, TERF1 rs3863242, and TERT rs2736098 have no correlation with H 2 O 2 level in omethoate exposure workers. The aim of this study was to explore the association between genetic variations in telomere pathway genes and the level of hydrogen peroxide (H 2 O 2) in omethoate exposure workers. A total of 180 omethoate exposure workers and 115 healthy controls were recruited. The level of H 2 O 2 in plasma was determined with molybdenic acid colorimetry. Polymerase chain reaction and restriction fragment length was used to detect polymorphisms in POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242, and TERT rs2736098. The level of H 2 O 2 in exposure group (4.26 ± 0.71) was significantly higher than that in control group (3.29 ± 0.46). Generalized linear models indicated that risk factors for the increase H 2 O 2 level were exposure [β(95 % CI) = 0.951 (0.806, 1.096), P < 0.001] and AA + AT genotype in POT1 rs034794 [β(95 % CI) = 0.397 (0.049, 0.745), P = 0.025]. The increase H 2 O 2 level was associated with omethoate exposure and AA + AT genotypes in POT1 gene rs1034794. It provided a new idea that polymorphisms in telomere pathway genes may indirectly regulate telomere length by influencing oxidative stress. [ABSTRACT FROM AUTHOR]