Monogenic Etiology of Hypertension.

Monogenic hypertension encompasses a group of conditions wherein single gene mutations result in increased renal sodium reabsorption manifesting as low renin hypertension. As these diseases are rare, their contribution to hypertension in children and adolescents is often overlooked. Precise diagnosis is essential in those who have not been found to have more common identifiable causes of hypertension in adolescents, since treatment strategies for these rare conditions are specific and different from antihypertensive regimens for the other more common causes of hypertension in this age group. The objective of this review is to provide insight to the rare, monogenic forms of hypertension.

Vision Zero and Impaired Driving: Near and Longer-Term Opportunities for Preventing Death and Injuries.

Vision Zero involves the use of a systems approach to eliminate fatal and serious injuries from motor vehicle crashes by accommodating basic human limitations that lead to crashes through fundamental behavioral expectations, together with sound vehicle and road design. Alcohol-related crashes account for a significant proportion of motor vehicle crash death and injury and can be addressed in a safe road transport system. We look at near-term policy and program interventions that are known to motivate drivers to make safe drinking and driving decisions, and possibilities for using technology over the longer term to address risks resulting from driver impairment that is either inadvertent or willful high-risk behavior. From the Vision Zero perspective,"normal driving" refers to a situation where traffic and road users are operating as desired and planned. A driver in this normal driving envelope operates at a safe speed, wears a seat belt, focuses on the driving task, and is not impaired. A safe system accommodates human errors, mistakes, and misjudgments in the normal driving envelope. However, it may not be capable of compensating for deliberate violations and rule-breaking. A critical role of behavioral programs and policies is to motivate safe decisions by drivers and other road users and keep them in the normal driving envelope where they can be protected from unintentional errors by a safe system. While much progress has been made in developing and implementing impaired driving policies and programs, much potential remains in the their ability to motivate drivers to meet the fundamental expectations required in a safe system. Examples of behavioral programs and policies that have strong evidence of effectiveness but are underutilized in the U.S. include conducting periodic sobriety checkpoints, lowering the blood alcohol concentration limit for driving, and mandating the use of ignition interlock devices. While the specific interventions may differ, it is likely that the same situation of incomplete implementation of behavioral programs and policies - and consequent unrealized value to a comprehensive safe system - applies to many other nations. To reach the goal of zero deaths, a comprehensive Vision Zero program needs to address the problem of deliberate risk-taking, which can include driver impairment from alcohol or other causes and extend to dangerous and reckless driving. Advanced safety technologies offer a range of opportunities for this purpose. Cars available today and in the future will have a plethora of sensors that monitor circumstances inside and around the car. These systems can identify whether a driver is in their safe driving envelope and respond with interventions that are appropriate for the severity and nature of the risk. Interventions could range from those that are not perceivable to the driver, such as putting driver assist systems into active mode, to stronger steps such as limiting or preventing vehicle operation. Zero fatalities or serious injuries in motor vehicle crashes is possible with a systems approach that accommodates human errors and mistakes that occur with the normal driving envelope and incorporates effective responses to deliberate risk-taking outside of this envelope.

The Five "I" Framework of crash investigation: Linking investigation practices to safety reform.

Crash investigation is vital to the advancement of road safety, and it is a foundation for determining effective countermeasures and interventions for true road safety reform. However, the way in which road crash investigations are conducted substantially influences the quality of understanding and the effectiveness of responses. In crash investigations, we traditionally focus first on the question: "What caused this crash?" when it would be more efficient to ask immediately: "What could have prevented this crash?" or better yet, "What are all the ways this crash could have been prevented?" In this paper, we first explore a few common road crash investigation approaches where prosecution, retribution, or compensation are primary. We then examine investigation approaches where prevention is primary, especially investigations aimed at determining every point on the timeline preceding the crash where an intervention would have prevented the outcome, as illustrated by the Swiss Cheese Model. We draw from examples from the aviation industry, the occupational health and safety field, the U.S. National Transportation Safety Board (NTSB), and others, to identify strengths and weaknesses. We bring together good practices from several investigative approaches through the lens of diverse experiences in transportation safety and root-cause analysis to present a practical and proactive framework for road crash investigation. The Five "I" Framework provides guiding characteristics for prevention-focused safety investigations for road crashes: Immediate, In-Depth, Impartial, Independent, and Injury Prevention. The Five "I" Framework is a practical guide for investigations to move beyond crash causation to crash prevention, aligning with the Safe Systems Approach, Vision Zero, and the public health perspective. Rather than focusing primarily on on any single factor such as vehicle defect or driver error, it leads investigations to an array of countermeasures that involve collective action and systems change, and thus, to more effective road safety reform. Nevertheless, as a practical framework, it is the start (not the end) of discussions on how we can continue to move towards more multidisciplinary, collaborative, innovative, and ethical prevention efforts.

Association of serum copper (Cu) with cardiovascular mortality and all-cause mortality in a general population: a prospective cohort study.

BACKGROUND: Copper (Cu) homeostasis and Cu-induced cell death are gaining recognition as crucial processes in the pathogenesis of cardiovascular disease (CVD). Circulating Cu associated with CVD and mortality is yet to be fully elucidated. OBJECTIVE: This national prospective cohort study is to estimate relationship between serum Cu and the risk of CVD and all-cause mortality. METHODS: This study included participants from the National Health and Nutrition Examination Survey 2011-2016. Weighted Cox proportional hazards regression analysis and exposure-response curves were applied. RESULTS: This included 5,412 adults, representing 76,479,702 individuals. During a mean of 5.85 years of follow-up (31,653 person-years), 96 CVD and 356 all-cause mortality events occurred. Age and sex-adjusted survival curves showed that individuals with higher levels of serum Cu experienced increased CVD and all-cause death rates (tertiles, p < 0.05). Compared with the participant in tertile 1 of serum Cu (< 16.31 mol/L), those in tertile 3 (≥ 19.84 mol/L) were significantly associated with CVD mortality (HR: 7.06, 95%CI: 1.85,26.96), and all-cause mortality (HR: 2.84, 95% CI: 1.66,4.87). The dose-response curve indicated a linear relationship between serum Cu and CVD mortality (p -nonlinear = 0.48) and all-cause (p -nonlinear = 0.62). A meta-analysis included additional three prospective cohorts with 13,189 patients confirmed the association between higher serum Cu and CVD (HR: 2.08, 95% CI: 1.63,2.65) and all-cause mortality (HR: 1.89, 95%CI: 1.58,2.25). CONCLUSION: The present study suggests excessive serum Cu concentrations are associated with the risk of CVD and all-cause mortality in American adults. Our findings and the causal relationships require further investigation.

The causal relationship between breast cancer and frozen shoulder: A two-sample Mendelian randomization.

To investigate the causal relationship between breast cancer and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with breast cancer and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median (WME) and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between breast cancer and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results showed an OR (95% CI) of 1.02 (1.00-1.04), P = .048, indicating that breast cancer is a risk factor for a frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using two-sample MR analysis, and the results showed that the incidence of frozen shoulder was higher in breast cancer patients, suggesting that screening for frozen shoulder in breast cancer patients should be increased.

Platelet count and gastric cancer susceptibility: A Mendelian randomization study.

The objective of this study was to ascertain the potential causal linkage between platelet (PLT) counts and the incidence of gastric cancer (GC). This study employed a 2-sample Mendelian randomization (MR) approach, utilizing the inverse variance weighting, weighted median, and MR-Egger regression methodologies. The publicly accessible summary statistics dataset from the genome-wide association study pertaining to individuals of European ancestry (n = 145,648) was employed as the foundational resource for the exposure variable. Concomitantly, the non-cancer disease codes for GC (n = 6563), derived from individuals within the UK Biosample Bank, were utilized as the outcome measure. A set of 132 single-nucleotide polymorphisms exhibiting genome-wide significance were selected as instrumental variables, drawn from the genome-wide association studies focused on PLT counts. The application of the weighted median methodology yielded indications suggesting the possible absence of a causal relationship between PLT counts and GC (beta = 0.139, SE = 0.079, P = .077). Contrarily, the implementation of the inverse variance weighting technique produced results indicative of a potential causal relationship between PLT counts and GC (beta = 0.128, SE = 0.049, P = .009). The assessment of Cochran Q test and the scrutiny of funnel plots unveiled no discernible indications of heterogeneity or asymmetry, thus signifying the absence of directional pleiotropy. The outcomes derived from the MR analysis lend credence to the hypothesis that there exists a plausible causal relationship between erythrocyte pressure and an elevated susceptibility to gastric cancer.

Protective effect of uridine on atrial fibrillation: a Mendelian randomisation study.

Uridine, a pyrimidine nucleoside, is crucial in the synthesis of metabolites. According to observational studies, a higher plasma uridine level is associated with a lower risk of atrial fibrillation (AF). However, the casual relationship between uridine and AF is still unknown. In this study, we used the Mendelian randomisation (MR) approach to explore causality. Three genetic variants associated with uridine were identified from the Metabolomics GWAS server (7824 participants); summary-level datasets associated with AF were acquired from a genome-wide association study (GWAS) meta-analysis with 1,030,836 European participants (60,620 AF cases). We duplicated the MR analyses using datasets from AF HRC studies and the FinnGen Consortium, and then conducted a meta-analysis which combined the main results. The risk of AF was significantly associated with the genetically determined plasma uridine level (odds ratio [OR] 0.27; 95% confidence interval [CI] 0.16, 0.47; p = 2.39 × 10-6). The association remained consistent in the meta-analysis of the various datasets (OR 0.27; 95% CI 0.17, 0.42; p = 1.34 × 10-8). In conclusion, the plasma uridine level is inversely associated with the risk of AF. Raising the plasma uridine level may have prophylactic potential against AF.

Causality between urate levels with sarcopenia-related traits: a bi-directional Mendelian randomization study.

Background: Observational studies have suggested associations between serum urate levels and sarcopenia, but the causality underlying this correlation remains uncertain. The principal objective of this study is to investigate a causal relationship of serum urate levels with sarcopenia-related traits (hand grip strength, lean mass, walking pace) using bidirectional two-sample Mendelian randomization (MR) approach. The utilization of MR methodology serves to minimize bias caused by reverse causality and confounding factors from observational studies. Methods: The summary statistics of serum urate levels were derived from a cohort consisting of 288,659 individuals participating in CKDGen study. The parameters of right-hand grip strength (N=461,089), left-hand grip strength (N=461,026), appendicular lean mass (ALM) (N=450,243), whole-body lean mass(N=454,850),right-leg fat-free mass(FFM;N=454,835),left-leg FFM(N=454,805), right-arm FFM(N=454,753),left-arm FFM(N=454,672) and walking pace (N=459,915)were sourced from the UK Biobank. MR analysis was conducted utilizing inverse variance weighted (IVW), weighted median, and MR-Egger to evaluate causality. Sensitivity analysis was performed using Cochran's Q test, MR-Egger intercept test, leave-one-out analysis and the funnel plot. Results: IVW estimates demonstrated that serum urate levels exhibited no causal association with sarcopenia-related traits. In the inverse MR investigation, we had exclusively discerned an inverse correlation between walking pace and serum urate levels. No compelling evidence had surfaced to substantiate any association of other sarcopenia-related traits with serum urate. Supplemental MR methods consistently validated the findings obtained from the primary analysis. Sensitivity analysis demonstrated the robustness of findings. Conclusion: Our MR study revealed the absence of the bidirectional causal relationship between serum urate levels and sarcopenia. It is imperative to acknowledge that advanced age and an individual's health status are pivotal determinants influencing urate level and the initiation and advancement of sarcopenia. However, it is worth underscoring that these aspects remain unexamined within the purview of this study. Thus, future investigations should delve deeper into these intricate facets.

Causation in different scientific disciplines: A comparison of standards in occupational medicine and particle physics.

Occupational medical research involves the collection and analysis of data to draw conclusions about the causes and prevention of workplace injuries and diseases. However, there has been criticism that some studies lack rigour in determining causation. This article examines the similarities and differences between occupational medical research and particle physics in terms of their approach to hypothesis testing, statistical methods, and confounder control. The article also explores the use of criteria such as the Bradford Hill criteria to determine causation in occupational medical research. While particle physics is often viewed as a highly rigorous science, occupational medical research also employs rigorous scientific methods to ensure findings are accurate and reliable. However, there is room for improvement in determining causation in occupational medical research, particularly in the use of criteria such as the Bradford Hill criteria to guide the development of more robust studies. It is essential for occupational medical research to adhere to rigorous scientific methods to deliver findings that can help reduce workplace injuries and diseases. The use of criteria such as the Bradford Hill criteria can ensure that the conclusions drawn. Med Pr Work Health Saf. 2023;74(4):333-9.

Environmental neurology: Concepts and short history of an interdisciplinary approach to etiology, treatment and prevention.

Environmental Neurology (EN), a sub-discipline of Neurology and Neurological Sciences, favors an interdisciplinary collaboration allowing a holistic approach to understanding the impact of environmental factors on the nervous system and their relationship with neurological diseases. Several examples of diseases and conditions show the large scope of subjects addressed by EN. The EN sub-discipline focuses on both individual and population issues thus joining patient care and public health, respectively. Neuropathogenesis is addressed by several major questions: How do the environment and nervous system interact? Which exogenous factors can trigger neurological disease? When, where and how do they act? What are the therapeutic implications, and how can these disorders be controlled or prevented. To answer such questions, we address the incentive for, philosophy of and methods developed by EN, which seeks to safeguard Brain Health and, thus, the quality of life.

SIGNET: transcriptome-wide causal inference for gene regulatory networks.

Gene regulation plays an important role in understanding the mechanisms of human biology and diseases. However, inferring causal relationships between all genes is challenging due to the large number of genes in the transcriptome. Here, we present SIGNET (Statistical Inference on Gene Regulatory Networks), a flexible software package that reveals networks of causal regulation between genes built upon large-scale transcriptomic and genotypic data at the population level. Like Mendelian randomization, SIGNET uses genotypic variants as natural instrumental variables to establish such causal relationships but constructs a transcriptome-wide gene regulatory network with high confidence. SIGNET makes such a computationally heavy task feasible by deploying a well-designed statistical algorithm over a parallel computing environment. It also provides a user-friendly interface allowing for parameter tuning, efficient parallel computing scheduling, interactive network visualization, and confirmatory results retrieval. The Open source SIGNET software is freely available ( https://www.zstats.org/signet/ ).

Interpreting and coding causal relationships for quality and safety using ICD-11.

Many circumstances necessitate judgments regarding causation in health information systems, but these can be tricky in medicine and epidemiology. In this article, we reflect on what the ICD-11 Reference Guide provides on coding for causation and judging when relationships between clinical concepts are causal. Based on the use of different types of codes and the development of a new mechanism for coding potential causal relationships, the ICD-11 provides an in-depth transformation of coding expectations as compared to ICD-10. An essential part of the causal relationship interpretation relies on the presence of "connecting terms," key elements in assessing the level of certainty regarding a potential relationship and how to proceed in coding a causal relationship using the new ICD-11 coding convention of postcoordination (i.e., clustering of codes). In addition, determining causation involves using documentation from healthcare providers, which is the foundation for coding health information. The coding guidelines and examples (taken from the quality and patient safety domain) presented in this article underline how new ICD-11 features and coding rules will enhance future health information systems and healthcare.

DHA Shortage Causes the Early Degeneration of Photoreceptors and RPE in Mice With Peroxisomal ß-Oxidation Deficiency.

Purpose: Patients deficient in peroxisomal ß-oxidation, which is essential for the synthesis of docosahexaenoic acid (DHA, C22:6n-3) and breakdown of very-long-chain polyunsaturated fatty acids (VLC-PUFAs), both important components of photoreceptor outer segments, develop retinopathy present with retinopathy. The representative mouse model lacking the central enzyme of this pathway, multifunctional protein 2 (Mfp2-/-), also show early-onset retinal decay and cell-autonomous retinal pigment epithelium (RPE) degeneration, accompanied by reduced plasma and retinal DHA levels. In this study, we investigated whether DHA supplementation can rescue the retinal degeneration of Mfp2-/- mice. Methods: Mfp2+/- breeding pairs and their offspring were fed a 0.12% DHA or control diet during gestation and lactation and until sacrifice. Offspring were analyzed for retinal function via electroretinograms and for lipid composition of neural retina and plasma with lipidome analysis and gas chromatography, respectively, and histologically using retinal sections and RPE flatmounts at the ages of 4, 8, and 16 weeks. Results: DHA supplementation to Mfp2-/- mice restored retinal DHA levels and prevented photoreceptor shortening, death, and impaired functioning until 8 weeks. In addition, rescue of retinal DHA levels temporarily improved the ability of the RPE to phagocytose outer segments and delayed the RPE dedifferentiation. However, despite the initial rescue of retinal integrity, DHA supplementation could not prevent retinal degeneration at 16 weeks. Conclusions: We reveal that the shortage of a systemic supply of DHA is pivotal for the early retinal degeneration in Mfp2-/- mice. Furthermore, we report that adequate retinal DHA levels are essential not only for photoreceptors but also for RPE homeostasis.

Exploring the causal relationship between inflammatory cytokines and migraine: a bidirectional, two-sample Mendelian randomization study.

To further evaluate the causal relationships between inflammatory cytokines and migraine, we conducted a bidirectional, two-sample Mendelian randomization (MR) analysis using genetic data from publicly available genome-wide association studies (GWAS). We used several MR methods, including random-effect inverse-variance weighting (IVW), weighted median, MR-Egger, to test the causal relationships. Sensitivity analyses were also conducted to evaluate the robustness of the results. The results showed that hepatocyte growth factor (HGF) was positively associated with the risk of migraine (odds ratio [OR], 1.004; 95% confidence interval [CI], 1.001-1.008; P = 0.022). In addition, Interleukin-2 (IL-2) was considered a downstream consequence of migraine (OR, 0.012; 95% CI, 0.000-0.0929; P = 0.046). These findings suggest that HGF may be a factor associated with the etiology of migraine, while IL-2 is more likely to be involved in the downstream development of migraine.

Causal relationship between dried fruit intake and frozen shoulder: Two-sample Mendelian randomization.

To investigate the causal relationship between dried fruit intake and frozen shoulder using Mendelian randomization (MR). Genome wide association studies were conducted to pool data and select genetic loci independently associated with dried fruit intake and frozen shoulder in people of European ancestry as instrumental variables. Three MR analyses, inverse variance weighting, weighted median and MR-Egger, were used to investigate the causal relationship between dried fruit intake and frozen shoulder. Heterogeneity and multiplicity tests were used, and sensitivity analyses were conducted using the leave-one-out method to explore the robustness of the results. The inverse variance weighting results showed an OR (95 % CI) of 0.52 (0.34-0.80), P = .003, suggesting that there is a causal relationship between dried fruit intake and frozen shoulder. And no heterogeneity and multiplicity were found by the test and sensitivity analysis also showed robust results. The present study used a two-sample MR analysis, and by analyzing and exploring the genetic data, the study showed that too little intake of dry fruits is a risk factor for developing frozen shoulder.

Occupational Etiology of Oropharyngeal Cancer: A Literature Review.

While abundant evidence exists linking alcohol, tobacco, and HPV infection to a carcinogenic impact on the oropharynx, the contribution of inhalational workplace hazards remains ill-defined. We aim to determine whether the literature reveals occupational environments at a higher-than-average risk of developing oropharyngeal cancer (OPC) and summarize the available data. To identify studies assessing the relationship between occupational exposure and risk of OPC, a search of the literature through the PubMed-NCBI database was carried out and, ultimately, 15 original articles meeting eligibility criteria were selected. Only original articles in English focusing on the association between occupational exposure and risk or death of specifically OPC were included. The available data are supportive of a potentially increased risk of OPC in waiters, cooks and stewards, artistic workers, poultry and meat workers, mechanics, and World Trade Center responders exposed to dust. However, the available literature on occupation-related OPC is limited. To identify occupational categories at risk, large cohorts with long follow-ups are needed. Identification of causal associations with occupation-related factors would require dose-response analyses adequately adjusted for confounders.

Rehabilitation Modulates High-Order Interactions Among Large-Scale Brain Networks in Subacute Stroke.

The recovery of motor functions after stroke is fostered by the functional integration of large-scale brain networks, including the motor network (MN) and high-order cognitive controls networks, such as the default mode (DMN) and executive control (ECN) networks. In this paper, electroencephalography signals are used to investigate interactions among these three resting state networks (RSNs) in subacute stroke patients after motor rehabilitation. A novel metric, the O-information rate (OIR), is used to quantify the balance between redundancy and synergy in the complex high-order interactions among RSNs, as well as its causal decomposition to identify the direction of information flow. The paper also employs conditional spectral Granger causality to assess pairwise directed functional connectivity between RSNs. After rehabilitation, a synergy increase among these RSNs is found, especially driven by MN. From the pairwise description, a reduced directed functional connectivity towards MN is enhanced after treatment. Besides, inter-network connectivity changes are associated with motor recovery, for which the mediation role of ECN seems to play a relevant role, both from pairwise and high-order interactions perspective.

Risk correlation identification of futures market based on wavelet transform and quantile Granger causality test.

Futures market is an important part of the financial market, with a high degree of liquidity and leverage effect. However, the futures market is also faced with various risk factors, such as price fluctuations, market shocks, supply and demand changes. In order to better determine the risk correlation between specific futures markets, this paper uses the wavelet transform-quantile Granger causality test method to identify the risk correlation of four major futures markets in the US futures market from the end of January 2009 to the end of March 2023, such as gold, crude oil, soybeans and natural gas. It provides a new perspective and method for the risk correlation identification of the futures market. The results show that futures contracts with different maturities and price fluctuations under different quantiles have a significant impact on risk correlation. Specifically, in 1-month and 6-month futures contracts, the strongest bidirectional risk correlation exists between gold and natural gas (T-statistics -15.94 and 10.92, respectively); In the 1-month futures contract, there is also a strong bidirectional risk association between crude oil and soybeans and natural gas (T-statistics are 6.87, 17.42, -2.05, 7.35, respectively), while in the 6-month futures contract, there is a bidirectional risk association between crude oil and soybeans (T-statistics are -2.49 and 18.374, respectively). However, natural gas has unidirectional risk association with crude oil and soybean (t statistics are 2.7 and -3.35, respectively); There is a bidirectional risk correlation between gold and soybean, that is, the risk correlation between gold and soybean increases with the increase of the degree of price fluctuation; There is a one-way risk association between gold and crude oil, soybean and gold, and crude oil and natural gas (the T-statistic is greater than the critical value of 1.96). In addition, there is a strong bidirectional or unidirectional risk association between all varieties at the 0.95 quantile. The research results of this paper have certain reference value for the supervision, investment and risk management of the futures market. This paper uses the wavelet transform and quantile Granger causality test method to identify the risk correlation of the futures market, providing a new perspective and method for the risk correlation identification of the futures market, and uses relatively new data to ensure the effectiveness of the empirical analysis. However, there are some limitations in this paper, such as the applicability of wavelet transform-quantile Granger causality test method. Future studies can further expand the sample range, compare the effects of different methods, and explore the risk transmission mechanism between different varieties.

Population impact of fine particulate matter on tuberculosis risk in China: a causal inference.

BACKGROUND: Previous studies have suggested the potential association between air pollution and tuberculosis incidence, but this association remains inconclusive and evidence to assess causality is particularly lacking. We aimed to draw causal inference between fine particulate matter less than 2.5 µm in diameter (PM2.5) and tuberculosis in China. METHODS: Granger causality (GC) inference was performed within vector autoregressive models at levels and/or first-differences using annual national aggregated data during 1982-2019, annual provincial aggregated data during 1982-2019 and monthly provincial aggregated data during 2004-2018. Convergent cross-mapping (CCM) approach was used to determine the backbone nonlinear causal association based on the monthly provincial aggregated data during 2004-2018. Moreover, distributed lag nonlinear model (DLNM) was applied to quantify the causal effects. RESULTS: GC tests identified PM2.5 driving tuberculosis dynamics at national and provincial levels in Granger sense. Empirical dynamic modeling provided the CCM causal intensity of PM2.5 effect on tuberculosis at provincial level and demonstrated that PM2.5 had a positive effect on tuberculosis incidence. Then, DLNM estimation demonstrated that the PM2.5 exposure driven tuberculosis risk was concentration- and time-dependent in a nonlinear manner. This result still held in the multi-pollutant model. CONCLUSIONS: Causal inference showed that PM2.5 exposure driving tuberculosis, which showing a concentration gradient change. Air pollutant control may have potential public health benefit of decreasing tuberculosis burden.