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oai:figshare.com:article/34024634 2026-09-29T14:43:51Z category_1 category_8 category_13 category_21 category_272 category_873 category_39 category_46 category_132 portal_63 item_type_6 month_year_09_2026

Genetic Evidence and Immunological Mechanisms Underlying the Link between Air Pollution and Rheumatic Arthropathies Jia-Chen Liu (11551168) Xiao-Rui Qiu (11551171) Zixi Jiang (15450982) Yantao Xu (9772521) Biophysics Microbiology Genetics Biotechnology Environmental Sciences not elsewhere classified Chemical Sciences not elsewhere classified Ecology Immunology Infectious Diseases uncover potential mediators systemic lupus erythematosus systematically evaluated associations shared causal locus mediated joint diseases colocalization analysis identified based sensitivity checks analyses included variant specific genetic architecture immunological mechanisms underlying immune trait profiling associated surface proteins ambient air pollution 5 </ sub 2 </ sub air pollution immunological insights genetic evidence significant association rheumatoid arthritis rheumatic arthropathies mechanistic pathways matrix metalloproteinase level overlap knee osteoarthritis juvenile arthritis inflammatory traits inflammatory markers increased risk including myeloid human health findings underscore environmental exposures 800 immune Accumulating epidemiological evidence suggests associations between ambient air pollution and rheumatic arthropathies, yet the underlying biological mechanisms remain elusive. We conducted a comprehensive genetic investigation linking five major air pollutants (PM₂.₅, PM₂.₅–₁₀, PM₁₀, NO₂, NO<i>_x</i>) with ten clinically defined rheumatic arthropathies. Using integrative genetic approaches, we systematically evaluated associations with over 800 immune and inflammatory traits to uncover potential mediators and mechanistic pathways. Analyses included variant-level overlap, immune trait profiling, and pathway-based sensitivity checks. Higher genetically proxied PM₂.₅ exposure was associated with increased risk of gout, rheumatoid arthritis, monoarthritis, and systemic lupus erythematosus. NO₂ exposure showed a significant association with juvenile arthritis. Colocalization analysis identified a shared causal locus (rs12203592) between PM₂.₅ exposure and knee osteoarthritis, suggesting a disease-specific genetic architecture. Mediation analysis identified six significant pollutant–mediator–disease pathways involving five immune/inflammatory markers, including myeloid- and lymphocyte-associated surface proteins and matrix metalloproteinase-1. This study provides novel genomic and immunological insights into how ambient air pollution contributes to the development of rheumatic arthropathies through immune–inflammatory mechanisms. Our findings underscore the relevance of environmental exposures in immune-mediated joint diseases and support the One Health framework linking environmental and human health. 2026-09-29T00:00:00Z Text Journal contribution 10.1021/envhealth.5c00488.s001 https://figshare.com/articles/journal_contribution/Genetic_Evidence_and_Immunological_Mechanisms_Underlying_the_Link_between_Air_Pollution_and_Rheumatic_Arthropathies/34024634 CC BY-NC 4.0