Multi-trait and multi-ancestry genetic analysis of comorbid lung diseases and traits improves genetic discovery and polygenic risk prediction.

While respiratory diseases such as COPD and asthma share many risk factors, most studies investigate them in insolation and in predominantly European ancestry populations. Here, we conducted the most powerful multi-trait and -ancestry genetic analysis of respiratory diseases and auxiliary traits to date. Our approach improves the power of genetic discovery across traits and ancestries, identifying 44 novel loci associated with lung function in individuals of East Asian ancestry. Using these results, we developed PRSxtra (cross TRait and Ancestry), a multi-trait and -ancestry polygenic risk score approach that leverages shared components of heritable risk via pleiotropic effects. PRSxtra significantly improved the prediction of asthma, COPD, and lung cancer compared to trait- and ancestry-matched PRS in a multi-ancestry cohort from the All of Us Research Program, especially in diverse populations. PRSxtra identified individuals in the top decile with over four-fold odds of asthma and COPD compared to the first decile. Our results present a new framework for multi-trait and -ancestry studies of respiratory diseases to improve genetic discovery and polygenic prediction.

Understanding the differential impact of PFOS and F-53B pollution on reed-mediated soil organic matter decomposition: Insights from rhizosphere priming effect.

Plants affect soil microorganisms through the release of root exudates under pollution stress. This process may affect rhizosphere priming effect (RPE) and alter the rate of soil organic matter decomposition. However, the influence of plants on the decomposition of organic matter in soil subjected to pollution stress remains unclear. We studied the effects of exposure to perfluorooctanesulfonic (PFOS) and its alternative, chlorinated polyfluoroalkyl ether sulfonic (F-53B), at concentrations of 0.1 mg/kg and 50 mg/kg on the RPE of reed. We conducted our experiments in an artificial climate chamber and used the natural 13C tracer method to determine RPE. In the PFOS-exposed groups, the RPE was negative, with values of -11.45 mg C kg-1 soil d-1 in the low PFOS group and -8.04 mg C kg-1 soil d-1 in the high PFOS group. In contrast, in the F-53B-exposed groups, the RPE was positive, with values of 8.26 mg C kg-1 soil d-1 in the low F-53B group and 12.18 mg C kg-1 soil d-1 in the high F-53B group. Exposure of reeds to PFOS/F-53B stress resulted in differential effects on extracellular enzyme activities. The observed positive and negative RPE phenomena could be attributed to variations in extracellular enzyme activities. In conclusion, RPE responded differently under PFOS/F-53B exposure.

Genetic architecture and socio-environmental risk factors for major depressive disorder in Nepal.

BACKGROUND: Major depressive disorder (MDD) is the leading cause of disability globally, with moderate heritability and well-established socio-environmental risk factors. Genetic studies have been mostly restricted to European settings, with polygenic scores (PGS) demonstrating low portability across diverse global populations. METHODS: This study examines genetic architecture, polygenic prediction, and socio-environmental correlates of MDD in a family-based sample of 10 032 individuals from Nepal with array genotyping data. We used genome-based restricted maximum likelihood to estimate heritability, applied S-LDXR to estimate the cross-ancestry genetic correlation between Nepalese and European samples, and modeled PGS trained on a GWAS meta-analysis of European and East Asian ancestry samples. RESULTS: We estimated the narrow-sense heritability of lifetime MDD in Nepal to be 0.26 (95% CI 0.18-0.34, p = 8.5 × 10-6). Our analysis was underpowered to estimate the cross-ancestry genetic correlation (rg = 0.26, 95% CI -0.29 to 0.81). MDD risk was associated with higher age (beta = 0.071, 95% CI 0.06-0.08), female sex (beta = 0.160, 95% CI 0.15-0.17), and childhood exposure to potentially traumatic events (beta = 0.050, 95% CI 0.03-0.07), while neither the depression PGS (beta = 0.004, 95% CI -0.004 to 0.01) or its interaction with childhood trauma (beta = 0.007, 95% CI -0.01 to 0.03) were strongly associated with MDD. CONCLUSIONS: Estimates of lifetime MDD heritability in this Nepalese sample were similar to previous European ancestry samples, but PGS trained on European data did not predict MDD in this sample. This may be due to differences in ancestry-linked causal variants, differences in depression phenotyping between the training and target data, or setting-specific environmental factors that modulate genetic effects. Additional research among under-represented global populations will ensure equitable translation of genomic findings.

Enhancing the Flexural Strength of AlN with an Additional Cross-Linking Mechanism in the Aqueous Isobam Gelling System.

Isobam is widely used for fabricating ceramics through spontaneous gelation and has attracted considerable interest. However, the disadvantage of the Isobam system is the low gelation strength. The effects of suitable additives and the mechanism by which they effectively enhance the green body strength and the rheological behavior of an aluminum nitride (AlN) slurry with 50 vol% solid loading were investigated using polyethyleneimine (PEI), hydantoin epoxy resin, and trimethylolpropane triglycidyl ether (TMPGE). Results showed that the additives acted as both dispersants and cross-linkers in the AlN suspension using the Isobam gelling system. The flexural strength of the AlN green body increased by 42%, 204%, and 268% with the addition of 1 wt% PEI, 1 wt% hydantoin epoxy resin, and 0.5 wt% TMPGE, respectively. After sintering at 1700 °C, the AlN ceramic with 0.5 wt% TMPGE had flexural strength and thermal conductivity of 235 MPa and 166.44 W/(m·K), respectively, showing superior performance to the ceramics without additives.

Impact of Serious Games on Body Composition, Physical Activity, and Dietary Change in Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Over the past four decades, obesity in children of all ages has increased worldwide, which has intensified the search for innovative intervention strategies. Serious games, a youth-friendly form of intervention designed with educational or behavioral goals, are emerging as a potential solution to this health challenge. To analyze the effectiveness of serious games in improving body composition, physical activity, and dietary change, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) from PubMed, Web of Science, EMBASE, and Scopus databases. Pooled standardized mean differences (SMD) were calculated for 20 studies (n = 2238 the intervention group; n = 1983 in the control group) using random-effect models. The intervention group demonstrated a slightly better, although non-significant, body composition score, with a pooled SMD of -0.26 (95% CI: -0.61 to 0.09). The pooled effect tends to be stronger with longer duration of intervention (-0.40 [95% CI: -0.96, 0.16] for >3 months vs. -0.02 [95% CI: -0.33, 0.30] for ≤3 months), although the difference was not statistically significant (p-difference = 0.24). As for the specific pathways leading to better weight control, improvements in dietary habits due to serious game interventions were not significant, while a direct positive effect of serious games on increasing physical activity was observed (pooled SMD = 0.61 [95% CI: 0.04 to 1.19]). While the impact of serious game interventions on body composition and dietary changes is limited, their effectiveness in increasing physical activity is notable. Serious games show potential as tools for overweight/obesity control among children and adolescents but may require longer intervention to sustain its effect.

Implications of Race Adjustment in Lung-Function Equations.

BACKGROUND: Adjustment for race is discouraged in lung-function testing, but the implications of adopting race-neutral equations have not been comprehensively quantified. METHODS: We obtained longitudinal data from 369,077 participants in the National Health and Nutrition Examination Survey, U.K. Biobank, the Multi-Ethnic Study of Atherosclerosis, and the Organ Procurement and Transplantation Network. Using these data, we compared the race-based 2012 Global Lung Function Initiative (GLI-2012) equations with race-neutral equations introduced in 2022 (GLI-Global). Evaluated outcomes included national projections of clinical, occupational, and financial reclassifications; individual lung-allocation scores for transplantation priority; and concordance statistics (C statistics) for clinical prediction tasks. RESULTS: Among the 249 million persons in the United States between 6 and 79 years of age who are able to produce high-quality spirometric results, the use of GLI-Global equations may reclassify ventilatory impairment for 12.5 million persons, medical impairment ratings for 8.16 million, occupational eligibility for 2.28 million, grading of chronic obstructive pulmonary disease for 2.05 million, and military disability compensation for 413,000. These potential changes differed according to race; for example, classifications of nonobstructive ventilatory impairment may change dramatically, increasing 141% (95% confidence interval [CI], 113 to 169) among Black persons and decreasing 69% (95% CI, 63 to 74) among White persons. Annual disability payments may increase by more than $1 billion among Black veterans and decrease by $0.5 billion among White veterans. GLI-2012 and GLI-Global equations had similar discriminative accuracy with regard to respiratory symptoms, health care utilization, new-onset disease, death from any cause, death related to respiratory disease, and death among persons on a transplant waiting list, with differences in C statistics ranging from -0.008 to 0.011. CONCLUSIONS: The use of race-based and race-neutral equations generated similarly accurate predictions of respiratory outcomes but assigned different disease classifications, occupational eligibility, and disability compensation for millions of persons, with effects diverging according to race. (Funded by the National Heart Lung and Blood Institute and the National Institute of Environmental Health Sciences.).

Aspiring toward equitable benefits from genomic advances to individuals of ancestrally diverse backgrounds.

Advancements in genomic technologies have shown remarkable promise for improving health trajectories. The Human Genome Project has catalyzed the integration of genomic tools into clinical practice, such as disease risk assessment, prenatal testing and reproductive genomics, cancer diagnostics and prognostication, and therapeutic decision making. Despite the promise of genomic technologies, their full potential remains untapped without including individuals of diverse ancestries and integrating social determinants of health (SDOHs). The NHGRI launched the 2020 Strategic Vision with ten bold predictions by 2030, including "individuals from ancestrally diverse backgrounds will benefit equitably from advances in human genomics." Meeting this goal requires a holistic approach that brings together genomic advancements with careful consideration to healthcare access as well as SDOHs to ensure that translation of genetics research is inclusive, affordable, and accessible and ultimately narrows rather than widens health disparities. With this prediction in mind, this review delves into the two paramount applications of genetic testing-reproductive genomics and precision oncology. When discussing these applications of genomic advancements, we evaluate current accessibility limitations, highlight challenges in achieving representativeness, and propose paths forward to realize the ultimate goal of their equitable applications.

Effect of branched 1,4-butanediol citrate oligomers with different molecular weights on toughness and aging resistance of glycerol plasticized starch.

The thermoplastic starch with glycerol is easy to retrograde and sensitive to hygroscopicity. In this study, branched 1,4-butanediol citrate oligomers with different molecular weights (P1, P2, and P3) are synthesized, and then mixed with glycerol (G) as the co-plasticizers to prepare thermoplastic starch (CS/PG). The results show that the molecular weight and branching degree of the branched 1,4-butanediol citrate oligomers increase as reaction time prolongs. Compared with glycerol plasticized starch, the thermoplastic starch films with branched 1,4-butanediol citrate oligomers/glycerol (10 wt%/20 wt%) have a better toughness, transmittance, and aging resistance, and have a lower crystallinity, hygroscopicity, and thermal stability. The toughness, transmittance, and aging resistance of CS/PG films are positively correlated with the molecular weight of the branched 1,4-butanediol citrate oligomers. These are due to the fact that the branched 1,4-butanediol citrate oligomer with a high molecular weight could form a stronger hydrogen bond and the more stable cross-linked structure with starch chains than that with a lower molecular weight. The elongation at break of CS/P3G film stored for 3 and 30 d are 98.0 % and 88.1 %, respectively. The mixture of branched butanediol citrate oligomers and glycerol, especially P3/G, has a potential application in the preparation of thermoplastic starch.

Association between the gut microbiota, inflammatory factors, and colorectal cancer: evidence from Mendelian randomization analysis.

Background: Colorectal cancer (CRC) is one of the most common malignant tumors primarily affecting individuals over the age of 50 years. Recent studies have suggested that the dysbiosis of the gut microbiota, a community of microorganisms in the human gut, is closely associated with the occurrence and development of CRC. Additionally, inflammatory factors (IFs) have also been reported to play a significant role in the development of CRC. However, the causal relationships between the gut microbiota, IFs, and CRC remain unclear. Methods: In this study, we performed Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) data to explore the causal relationship between the gut microbiota, IFs, and CRC. The gut microbiota GWAS data were obtained from the MiBioGen study, while the IFs GWAS data were derived from the comprehensive analysis of three independent cohorts. Causal relationship analysis was conducted using appropriate instrumental variables (IVs) and statistical models. Results: MR analysis of the gut microbiota and CRC revealed a negative correlation between the Lachnospiraceae species in the gut and CRC risk, while a positive correlation was observed between Porphyromonadaceae species, Lachnospiraceae UCG010 genus, Lachnospira genus, and Sellimonas genus in the gut, and CRC risk. Additionally, we observed a causal relationship between IL-10 and CRC risk. These findings suggest that the dysbiosis of the gut microbiota might be associated with an increased risk of CRC and that specific bacterial groups may play a crucial role in the occurrence and development of CRC. Conclusion: Using MR analysis, this study revealed the causal relationships between the gut microbiota, IFs, and CRC. The negative correlation between the Lachnospiraceae species in the gut and CRC risk, as well as the causal relationship between IL-10 and CRC, provide important clues for the potential roles of gut microbiota regulation and inflammatory factor control in the prevention and treatment of CRC.

Patterns of Undertreatment and Overtreatment in Adjuvant Radiotherapy for Early-Stage Endometrial Cancer Based on Molecular Classification.

The quality improvement study examines the use of risk-adaptive adjuvant radiotherapy in women with non­mismatch repair deficiency endometrial cancer.

Integrated analysis of disulfidptosis-related immune genes signature to boost the efficacy of prognostic prediction in gastric cancer.

BACKGROUND: Gastric cancer (GC) remains a malignant tumor with high morbidity and mortality, accounting for approximately 1,080,000 diagnosed cases and 770,000 deaths worldwide annually. Disulfidptosis, characterized by the stress-induced abnormal accumulation of disulfide, is a recently identified form of programmed cell death. Substantial studies have demonstrated the significant influence of immune clearance on tumor progression. Therefore, we aimed to explore the intrinsic correlations between disulfidptosis and immune-related genes (IRGs) in GC, as well as the potential value of disulfidptosis-related immune genes (DRIGs) as biomarkers. METHODS: This study incorporated the single-cell RNA sequencing (scRNA-seq) dataset GSE183904 and transcriptome RNA sequencing of GC from the TCGA database. Disulfidptosis-related genes (DRGs) and IRGs were derived from the representative literature on both cell disulfidptosis and immunity. The expression and distribution of DRGs were investigated at the single-cell level in different GC cell types. Pearson correlation analysis was used to identify the IRGs closely related to disulfidptosis. The prognostic signature of DRIGs was established using Cox and LASSO analyses. We then analyzed and evaluated the differences in long-term prognosis, Gene Set Enrichment Analysis (GSEA), immune infiltration, mutation profile, CD274 expression, and response to chemotherapeutic drugs between the two groups. A tissue array containing 63 paired GC specimens was used to verify the expression of 4 DRIGs and disulfidptosis regulator SLC7A11 through immunohistochemistry staining. RESULTS: The scRNA-seq analysis found that SLC7A11, SLC3A2, RPN1 and NCKAP1 were enriched in specific cell types and closely related to immune infiltration. Four DIRGs (GLA, HIF-1α, VPS35 and CDC37) were successfully identified to establish a signature to potently predict the survival time of GC patients. Patients with high risk scores generally experienced worse prognoses and exhibited greater resistant to classical chemotherapy drugs. Furthermore, the expression of GLA, HIF-1α, VPS35, CDC37 and SLC7A11 were elevated in GC tissues. A high expression of GLA, HIF-1α, VPS35 or CDC37 was associated with more advanced clinical stage of GC and increased SLC7A11 expression. CONCLUSION: Current study first highlights the potential value of DRIGs as biomarkers in GC. We successfully constructed a robust model incorporating four DRIGs to accurately predict the survival time and clinicopathological characteristics of GC patients.

Identification and validation of protein biomarkers for predicting gastrointestinal stromal tumor recurrence.

We conducted a proteomic analysis using mass spectrometry to identify and validate protein biomarkers for accurately predicting recurrence risk in gastrointestinal stromal tumors (GIST) patients, focusing on differentially expressed proteins in metastatic versus primary GIST tissues. We selected five biomarkers-GPX4, RBM4, TPM3, PFKFB2, and PGAM5-and validated their expressions in primary tumors of recurrent and non-recurrent GIST patients via immunohistochemistry. Our analysis of the association between these biomarkers with recurrence-free survival (RFS) and overall survival (OS), along with their interrelationships, revealed that immunohistochemistry confirmed significantly higher expressions of these biomarkers in primary GIST tissues of recurrent patients. Kaplan-Meier survival analysis showed that high expressions of GPX4, RBM4, TPM3, PFKFB2, and PGAM5 correlated with lower RFS, and GPX4 and RBM4 with lower OS. All biomarker pairs showed positive associations, with high expressions correlating with increased recurrence rates, and GPX4 and RBM4 with higher mortality rates. In conclusion, the biomarkers GPX4, RBM4, TPM3, PFKFB2, and PGAM5 are clinically relevant for predicting GIST recurrence, with their high expressions in primary tumors linked to poorer RFS and OS. They serve as potential prognostic indicators, enabling early treatment and improved outcomes. The observed interrelationships among these biomarkers further validate their accuracy in predicting GIST recurrence.

Assessing the genetic contribution of cumulative behavioral factors associated with longitudinal type 2 diabetes risk highlights adiposity and the brain-metabolic axis.

While genetic factors, behavior, and environmental exposures form a complex web of interrelated associations in type 2 diabetes (T2D), their interaction is poorly understood. Here, using data from ~500K participants of the UK Biobank, we identify the genetic determinants of a "polyexposure risk score" (PXS) a new risk factor that consists of an accumulation of 25 associated individual-level behaviors and environmental risk factors that predict longitudinal T2D incidence. PXS-T2D had a non-zero heritability (h2 = 0.18) extensive shared genetic architecture with established clinical and biological determinants of T2D, most prominently with body mass index (genetic correlation [rg] = 0.57) and Homeostatic Model Assessment for Insulin Resistance (rg = 0.51). Genetic loci associated with PXS-T2D were enriched for expression in the brain. Biobank scale data with genetic information illuminates how complex and cumulative exposures and behaviors as a whole impact T2D risk but whose biology have been elusive in genome-wide studies of T2D.

Peiminine alleviate coliti-like phenotype in mice induced by lead exposure.

The deleterious impact of lead (Pb) pollution on human health is evident in both domestic and occupational settings, provoking an inflammatory response across multiple tissue, limited attention has been devoted to its adverse effects on colitis and the underlying mechanisms. Peiminine (PMI) has been recognized for its anti-inflammatory properties, yet its specific anti-inflammatory effects in lead-induced colitis models remain elusive. Through the establishment of both in vivo and in vitro lead exposure models, suggests that lead exposure can induce colitis and that PMI regulates lead exposure-induced colitis by inhibiting the NF-kB signaling pathway, and alleviates the ability of lead to apoptosis and inflammation levels in intestinal epithelial cells. Consequently, these results present a promising avenue for further exploration of the molecular mechanisms underlying lead-induced colitis, evaluation of the associated risks linked to lead exposure, and the development of therapeutic interventions for colitis resulting from lead exposure.

The clustering status of detached gastric cancer cells inhibits anoikis-induced ferroptosis to promote metastatic colonization.

BACKGROUND AND PURPOSE: Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. Its role in cancer metastasis remains unclear. In this study, we aimed to investigate the potential involvement of ferroptosis in gastric cancer (GC) metastasis. METHODS: GC cells (AGS, MKN45, HGC27) were used to explore the role of ferroptosis in single and clustered cells with extracellular matrix (ECM) detachment in vitro. We overexpressed glutathione peroxidase 4 (GPX4) to inhibit ferroptosis and assessed the changes in cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Then tumor tissues from 54 GC patients with and without lymphatic metastasis were collected for immunohistochemical staining to investigate the expression of ferroptosis and EMT markers. Finally, Kaplan-Meier survival curves were used to investigate the relationship between overall survival and expression of GPX4 in 178 GC patients. RESULTS: Detached single cells had lower viability than adherent cells, but cell clustering improved their survival under matrix-detached conditions. Detached single cells exhibited an induction of iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of ACSL4, TFRC and HO-1, increased iron levels, and changes in mitochondrial morphology. Opposite effects were observed in detached clustered cells, including the upregulation of the ferroptosis suppressors GPX4 and SLC7A11. Overexpression of GPX4 inhibited ferroptosis and promoted GC cell proliferation, migration, invasion, and EMT. Immunohistochemical analysis of tumor tissues from GC patients indicated that lymphatic metastasis was associated with higher potential for ferroptosis inhibition and EMT induction. Finally, Kaplan-Meier survival curves demonstrated a significant decrease in overall survival among GC patients with high GPX4 expression. CONCLUSIONS: Our study provides the first evidence that inhibition of ferroptosis is a crucial mechanism promoting GC metastasis. GPX4 may be a valuable prognostic factor for GC patients. These findings suggest that targeting ferroptosis inhibition may be a promising strategy for GC patients with metastatic potential. Trial registration The ethical approval code of this study in Institutional Review Board of Peking Union Medical College Hospital is No: K1447.

ACE2 improves endothelial cell function and reduces acute lung injury by downregulating FAK expression.

Endothelial cell (EC) barrier dysfunction and increased adhesion of immune inflammatory cells to ECs crucially contribute to acute lung injury (ALI). Angiotensin-converting enzyme 2 (ACE2) is an essential regulator of the renin-angiotensin system (RAS) and exerts characteristic vasodilatory and anti-inflammatory effects. SARS-COV-2 infects the lungs by binding to ACE2, which can lead to dysregulation of ACE2 expression, further leading to ALI with predominantly vascular inflammation and eventually to more severe acute respiratory distress syndrome (ARDS). Therefore, restoration of ACE2 expression represents a valuable therapeutic approach for SARS-COV-2-related ALI/ARDS. In this study, we used polyinosinic-polycytidylic acid (Poly(I:C)), a double-stranded RNA analog, to construct a mouse ALI model that mimics virus infection. After Poly(I:C) exposure, ACE2 was downregulated in mouse lung tissues and in cultured ECs. Treatment with DIZE, an ACE2-activating compound, upregulated ACE2 expression and relieved ALI in mice. DIZE also improved barrier function and reduced the number of THP-1 monocytes adhering to cultured ECs. Focal adhesion kinase (FAK) and phosphorylated FAK (p-FAK) levels were increased in lung tissues of ALI mice as well as in Poly(I:C)-treated ECs in vitro. Both DIZE and the FAK inhibitor PF562271 decreased FAK/p-FAK expression in both ALI models, attenuating ALI severity in vivo and increasing barrier function and reducing monocyte adhesion in cultured ECs. Furthermore, in vivo experiments using ANG 1-7 and the MAS inhibitor A779 corroborated that DIZE-mediated ACE2 activation stimulated the activity of the ANG 1-7/MAS axis, which inhibited FAK/p-FAK expression in the mouse lung. These findings provide further evidence that activation of ACE2 in ECs may be a valuable therapeutic strategy for ALI.

Crosstalk between gut microbiota and gut resident macrophages in inflammatory bowel disease.

Macrophages residing in the gut maintain gut homeostasis by orchestrating patho-gens and innocuous antigens. A disturbance in macrophages leads to gut inflamma-tion, causing conditions such as inflammatory bowel disease (IBD). Macrophages ex-hibit remarkable plasticity, as they are sensitive to various signals in the tissue micro-environment. During the recent decades, gut microbiota has been highlighted refer-ring to their critical roles in immunity response. Microbiome-derived metabolites and products can interact with macrophages to participate in the progression of IBD. In this review, we describe recent findings in this field and provide an overview of the current understanding of microbiota-macrophages interactions in IBD, which may lead to the development of new targets and treatment options for patients with IBD.

Prediction and stratification of longitudinal risk for chronic obstructive pulmonary disease across smoking behaviors.

Smoking is the leading risk factor for chronic obstructive pulmonary disease (COPD) worldwide, yet many people who never smoke develop COPD. We perform a longitudinal analysis of COPD in the UK Biobank to derive and validate the Socioeconomic and Environmental Risk Score which captures additive and cumulative environmental, behavioral, and socioeconomic exposure risks beyond tobacco smoking. The Socioeconomic and Environmental Risk Score is more predictive of COPD than smoking status and pack-years. Individuals in the highest decile of the risk score have a greater risk for incident COPD compared to the remaining population. Never smokers in the highest decile of exposure risk are more likely to develop COPD than previous and current smokers in the lowest decile. In general, the prediction accuracy of the Social and Environmental Risk Score is lower in non-European populations. While smoking status is often considered in screening COPD, our finding highlights the importance of other non-smoking environmental and socioeconomic variables.