OBJECTIVES
The associations between ambient air pollution mixtures, related metabolic and proteomic signatures, and arthritis subtypes, including rheumatoid arthritis (RA), osteoarthritis (OA), gout, and psoriatic arthritis (PsA), remain unclear.
METHODS
This prospective cohort study included 401,676 UK Biobank participants free of arthritis at baseline. Air pollution mixture exposure was quantified using Weighted Quantile Sum (WQS) regression. Metabolic and proteomic signatures were derived using multivariable linear and elastic net regression. Associations with incident arthritis were evaluated using Cox proportional hazards models and generalized propensity score approaches. Causal mediation analysis was performed to assess mediating effects.
RESULTS
Over a median follow-up of 13 years, 78,188 any type of arthritis cases were identified. The primary contributors to the WQS mixture index were NOx and NO₂ for RA, PM2.5 for OA, NOx and PM2.5 for gout, and PM2.5 and PM10 for PsA. Higher WQS index scores and their associated metabolic and proteomic signatures were associated with increased risks of arthritis subtypes. These signatures mediated the associations between air pollution mixtures and arthritis risk, with mediation proportions ranging from 4.92% to 35.05%. Top 10 mediating metabolites and proteins showed partial overlap, alongside disease-specific profiles across arthritis subtypes.
CONCLUSION
Air pollution mixtures were associated with increased risks of arthritis subtypes, potentially through both shared and disease-specific metabolic and proteomic pathways, highlighting the importance of considering pollutant mixtures and disease heterogeneity in arthritis research and prevention.
Jin Feng, Xue-Na Yang, Shiqiang Cheng et al.· Joint Bone Spine· 0 citations
Abstract Background Although adolescent depression has been linked to individual chronic conditions, its broader role in shaping multimorbidity risk remains understudied. Methods A total of 87,562 UK Biobank participants were included, of whom 18,851 had documented adolescent depression. Cox proportional hazards models were applied to evaluate associations between adolescent depression and 24 chronic diseases, followed by stratified analyses by sex and age. Two-sample Mendelian randomization (MR) was then conducted to infer causality for diseases showing significant associations. Genomic colocalization analyses were performed using relevant GWAS data to identify shared causal variants. Mediation analyses were performed to detect possible mediating factors, including the frailty index, KDM biological age acceleration, allostatic load and 30 circulating biomarkers. Results Adolescent depression was associated with elevated risk for 12 chronic diseases, with strongest associations for hypothyroidism (HR = 1.29 [1.18–1.42]), diabetes (HR = 1.25 [1.13–1.38]) and chronic obstructive pulmonary disease (COPD) (HR = 1.74 [1.50–2.01]). Risks were notably higher among females and younger adults. MR confirmed likely causal relationships for hypothyroidism (OR = 1.45 [1.03–2.05]), diabetes (OR = 1.01 [1.01–1.02]) and COPD (OR = 1.04 [1.02–1.06]). Genomic colocalization revealed a shared genetic signal at the CDSN/PSORS1C1 locus between adolescent depression and hypothyroidism. Mediation analyses revealed disease-specific pathways: creatinine for hypothyroidism, testosterone for diabetes, KDM biological ageing for COPD and frailty index across all three conditions. Conclusions Adolescent depression confers systemic vulnerability through genetic and metabolic mechanisms, with amplified risks in females and individuals aged ≤55 years. These findings support early, integrated interventions to mitigate long-term multimorbidity.
Wen-Ming Wei, B. Cheng, X. Qi et al.· Epidemiology and Psychiatric...· 0 citations
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