{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:49:49Z","timestamp":1753886989722,"version":"3.40.5"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yunnan Provincial Health Commission Medical Discipline Leader Training Program","award":["D-2019026"],"award-info":[{"award-number":["D-2019026"]}]},{"name":"Kunming City Health Science and Technology Talent Development Program\u2014Leading Personnel Training Project in Medical Science and Technology Discipline","award":["2022-SW(Leading)-33"],"award-info":[{"award-number":["2022-SW(Leading)-33"]}]},{"name":"Yunnan Provincial Science and Technology Department Science and Technology Plan Project","award":["202401AY070001-159"],"award-info":[{"award-number":["202401AY070001-159"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Rheumatoid arthritis is a common rheumatic disease, and its onset is closely related to genetic and environmental factors, however, the relationship between air pollution and RA is still hotly debated. Further investigation of the relationship between air pollution and rheumatoid arthritis is conducive to a comprehensive understanding of the risk factors of the disease, providing certain value for the clinical prevention and treatment of RA.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We used a Two-Sample Mendelian Randomization approach, integrating the large-scale public genomewide association study, to assess the genetically predicted causal effect of air pollution (including: PM2.5, PM2.5\u201310, PM10, nitrogen dioxide, nitrogen oxides) on RA in European and <jats:strike>European<\/jats:strike> East Asian populations, respectively. Indicators related to air pollution (2,505 individuals to 423,796 individuals), including European and East Asian populations were obtained from the Integrative Epidemiology Unit open GWAS project. Published East Asian RA data were also obtained from the IEU open GWAS project (212,453 individuals), while large-scale publicly available European RA data were obtained from finngen R10 (13,621 cases and 262,844 controls). Inverse variance weighting was used as the primary analytical method, complemented by MR-egger, Weighed median, and Weighted mode results. Cochran Q tested for heterogeneity, and MR-Egger regression analyses were performed to test for multiplicity. leave-one-out analysis allowed for the robustness and reliability were assessed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>No statistically significant effects of PM2.5, PM2.5\u201310, PM10, nitrogen dioxide, nitrogen oxides and RA were observed in either European or East Asian populations. Results from European data: PM2.5 (IVW OR: 0.71; 95% CI: 0.27\u20131.91; p = 0.498; number of SNPs: 5), PM2.5\u201310 (IVW OR: 1.20; 95% CI: 0.61\u20132.40; p = 0.596; number of SNPs: 15), PM10 (IVW OR: 1.69; 95% CI: 0.84\u20133.39; p = 0.142; number of SNPs: 9), nitrogen dioxide (IVW OR: 3.88; 95% CI: 0.19\u201377.77; p = 0.375; number of SNPs: 2), nitrogen oxides (IVW OR: 0.51; 95% CI: 0.16\u20131.67; p = 0.268; number of SNPs: 4). East Asian data results: PM2.5 (IVW OR: 1.16; 95% CI: 0.98\u20131.38; p = 0.086; number of SNPs: 4), PM2.5\u201310 (IVW OR: 1.14; 95% CI: 0.95\u20131.38; p = 0.166; number of SNPs: 2), PM10 (IVW OR: 0.95; 95% CI: 0.81\u20131.11; p = 0.503; number of SNPs: 3), nitrogen dioxide (IVW OR: 0.87; 95% CI: 0.76\u20131.00; p = 0.051; number of SNPs: 6), nitrogen oxides (IVW OR: 0.96; 95% CI: 0.82\u20131.14; p = 0.671; number of SNPs: 3). No signs of pleiotropy or heterogeneity were observed in the MR-Egger intercept, MR-PRESSO and Cochrane\u2019s Q (p&gt;0.05). In addition, no outliers were found in the MR-PRESSO analysis. The results were further validated by leave-one-out tests, confirming the robustness of the findings.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We performed transethnic MR analysis suggesting that there may not be a genetically predicted causal relationship between air pollution and RA.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0307514","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T17:24:03Z","timestamp":1727198643000},"page":"e0307514","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Causal associations of air pollution with rheumatoid arthritis: A transethnic Mendelian randomization study"],"prefix":"10.1371","volume":"19","author":[{"given":"Ao","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hainan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingzhu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songmei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7789-2700","authenticated-orcid":true,"given":"Xian","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"issue":"19","key":"pone.0307514.ref001","first-page":"e2218019120","article-title":"Schnurri-3 inhibition suppresses bone and joint damage in models of rheumatoid arthritis","volume":"120","year":"2023","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"pone.0307514.ref002","doi-asserted-by":"crossref","first-page":"812631","DOI":"10.3389\/fcvm.2021.812631","article-title":"Effect of Anti-Rheumatic Drugs on Cardiovascular Disease Events in Rheumatoid Arthritis","volume":"8","author":"Y Baoqi","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"pone.0307514.ref003","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1097\/BOR.0000000000000782","article-title":"Racial, Ethnic, and Healthcare Disparities in Rheumatoid Arthritis","volume":"33","author":"K Yip","year":"2021","journal-title":"Curr Opin Rheumatol"},{"key":"pone.0307514.ref004","doi-asserted-by":"crossref","first-page":"A288","DOI":"10.1016\/j.autrev.2009.11.019","article-title":"The environment, geo-epidemiology, and autoimmune disease: Rheumatoid arthritis","volume":"9","author":"GJ Tob\u00f3n","year":"2010","journal-title":"Autoimmun Rev"},{"key":"pone.0307514.ref005","doi-asserted-by":"crossref","first-page":"122181","DOI":"10.1016\/j.envpol.2023.122181","article-title":"Potential roles of air pollutants on the induction and aggravation of rheumatoid arthritis: From cell to bedside studies","volume":"334","author":"W Gumtorntip","year":"2023","journal-title":"Environ Pollut"},{"key":"pone.0307514.ref006","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/aje\/kwm165","article-title":"The Impact of Residual and Unmeasured Confounding in Epidemiologic Studies: A Simulation Study","volume":"166","author":"Z Fewell","year":"2007","journal-title":"Am J Epidemiol"},{"key":"pone.0307514.ref007","doi-asserted-by":"crossref","first-page":"31303","DOI":"10.1289\/EHP12167","article-title":"Invited Perspective: Air Pollutants, Genetics, and the Mucosal Paradigm for Rheumatoid Arthritis Risk","volume":"131","author":"GC McDermott","year":"2023","journal-title":"Environ Health Perspect"},{"key":"pone.0307514.ref008","doi-asserted-by":"crossref","first-page":"115628","DOI":"10.1016\/j.envpol.2020.115628","article-title":"Association between traffic-related air pollution and hospital readmissions for rheumatoid arthritis in Hefei, China: A time-series study","volume":"268","author":"Q Wu","year":"2021","journal-title":"Environ Pollut"},{"key":"pone.0307514.ref009","doi-asserted-by":"crossref","first-page":"4591","DOI":"10.1093\/rheumatology\/keab049","article-title":"Association between environmental air pollution and rheumatoid arthritis flares","volume":"60","author":"G Adami","year":"2021","journal-title":"Rheumatology (Oxford)"},{"key":"pone.0307514.ref010","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1177\/0962280206077743","article-title":"Mendelian randomization as an instrumental variable approach to causal inference","volume":"16","author":"V Didelez","year":"2007","journal-title":"Stat Methods Med Res"},{"key":"pone.0307514.ref011","first-page":"690","article-title":"Mendelian Randomization Studies Promise to Shorten the Journey to FDA Approval","volume":"3","author":"R. Roberts","year":"2018","journal-title":"JACC: Basic to Translational Science"},{"key":"pone.0307514.ref012","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1177\/0962280210394459","article-title":"Using multiple genetic variants as instrumental variables for modifiable risk factors","volume":"21","author":"TM Palmer","year":"2012","journal-title":"Stat Methods Med Res"},{"key":"pone.0307514.ref013","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1002\/sim.3034","article-title":"Mendelian randomization: using genes as instruments for making causal inferences in epidemiology","volume":"27","author":"DA Lawlor","year":"2008","journal-title":"Stat Med"},{"key":"pone.0307514.ref014","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1681\/ASN.2016010098","article-title":"Mendelian Randomization as an Approach to Assess Causality Using Observational Data","volume":"27","author":"P Sekula","year":"2016","journal-title":"JASN"},{"key":"pone.0307514.ref015","doi-asserted-by":"crossref","first-page":"n2233","DOI":"10.1136\/bmj.n2233","article-title":"Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration","volume":"375","author":"VW Skrivankova","year":"2021","journal-title":"BMJ"},{"key":"pone.0307514.ref016","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1007\/s00011-023-01740-0","article-title":"Causal associations of circulating Helicobacter pylori antibodies with stroke and the mediating role of inflammation","volume":"72","author":"X Guo","year":"2023","journal-title":"Inflamm Res"},{"key":"pone.0307514.ref017","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data","volume":"37","author":"S Burgess","year":"2013","journal-title":"Genet Epidemiol"},{"key":"pone.0307514.ref018","doi-asserted-by":"crossref","first-page":"689698","DOI":"10.3389\/fmed.2021.689698","article-title":"Etiology and Risk Factors for Rheumatoid Arthritis: A State-of-the-Art Review","volume":"8","author":"VC Rom\u00e3o","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"pone.0307514.ref019","doi-asserted-by":"crossref","first-page":"13784","DOI":"10.1002\/cam4.6022","article-title":"Genetically predicted 486 blood metabolites in relation to risk of colorectal cancer: A Mendelian randomization study","volume":"12","author":"Z Yun","year":"2023","journal-title":"Cancer Medicine"},{"key":"pone.0307514.ref020","doi-asserted-by":"crossref","first-page":"e1007081","DOI":"10.1371\/journal.pgen.1007081","article-title":"Orienting the causal relationship between imprecisely measured traits using GWAS summary data","volume":"13","author":"G Hemani","year":"2017","journal-title":"PLoS Genet"},{"key":"pone.0307514.ref021","doi-asserted-by":"crossref","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"G Hemani","year":"2018","journal-title":"eLife"},{"key":"pone.0307514.ref022","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator","volume":"40","author":"J Bowden","year":"2016","journal-title":"Genetic Epidemiology"},{"key":"pone.0307514.ref023","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","article-title":"Interpreting findings from Mendelian randomization using the MR-Egger method","volume":"32","author":"S Burgess","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"pone.0307514.ref024","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"M Verbanck","year":"2018","journal-title":"Nat Genet"},{"key":"pone.0307514.ref025","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.jclinepi.2014.09.005","article-title":"Cochran\u2019s Q test was useful to assess heterogeneity in likelihood ratios in studies of diagnostic accuracy","volume":"68","author":"JF Cohen","year":"2015","journal-title":"J Clin Epidemiol"},{"key":"pone.0307514.ref026","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nature01661","article-title":"Evolving concepts of rheumatoid arthritis","volume":"423","author":"GS Firestein","year":"2003","journal-title":"Nature"},{"key":"pone.0307514.ref027","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"IB McInnes","year":"2011","journal-title":"N Engl J Med"},{"key":"pone.0307514.ref028","doi-asserted-by":"crossref","first-page":"e4035","DOI":"10.7717\/peerj.4035","article-title":"Characteristics and risk factors of rheumatoid arthritis in the United States: an NHANES analysis","volume":"5","author":"B Xu","year":"2017","journal-title":"PeerJ"},{"key":"pone.0307514.ref029","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.envint.2016.06.008","article-title":"Air pollution exposure increases the risk of rheumatoid arthritis: A longitudinal and nationwide study","volume":"94","author":"K-H Chang","year":"2016","journal-title":"Environment International"},{"key":"pone.0307514.ref030","doi-asserted-by":"crossref","first-page":"e002055","DOI":"10.1136\/rmdopen-2021-002055","article-title":"Association between long-term exposure to air pollution and immune-mediated diseases: a population-based cohort study","volume":"8","author":"G Adami","year":"2022","journal-title":"RMD Open"},{"key":"pone.0307514.ref031","doi-asserted-by":"crossref","first-page":"037008","DOI":"10.1289\/EHP10710","article-title":"Association of Combined Exposure to Ambient Air Pollutants, Genetic Risk, and Incident Rheumatoid Arthritis: A Prospective Cohort Study in the UK Biobank","volume":"131","author":"J Zhang","year":"2023","journal-title":"Environ Health Perspect"},{"key":"pone.0307514.ref032","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.semarthrit.2019.10.005","article-title":"Long-term exposure to outdoor air pollution and the risk of development of rheumatoid arthritis: A systematic review and meta-analysis","volume":"50","author":"D Di","year":"2020","journal-title":"Semin Arthritis Rheum"},{"key":"pone.0307514.ref033","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1136\/annrheumdis-2012-201587","article-title":"Ambient air pollution exposures and risk of rheumatoid arthritis: results from the Swedish EIRA case-control study","volume":"72","author":"JE Hart","year":"2013","journal-title":"Ann Rheum Dis"},{"key":"pone.0307514.ref034","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1136\/annrheumdis-2012-202949","article-title":"Relationship between air pollution and positivity of RA-related autoantibodies in individuals without established RA: a report on SERA","volume":"72","author":"RW Gan","year":"2013","journal-title":"Ann Rheum Dis"},{"key":"pone.0307514.ref035","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/EDE.0000000000000409","article-title":"Selection bias due to loss to follow up in cohort studies","volume":"27","author":"CJ Howe","year":"2016","journal-title":"Epidemiology"},{"key":"pone.0307514.ref036","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1023\/B:EJEP.0000036568.02655.f8","article-title":"Loss to follow-up in cohort studies: how much is too much?","volume":"19","author":"V Kristman","year":"2004","journal-title":"Eur J Epidemiol"},{"key":"pone.0307514.ref037","doi-asserted-by":"crossref","first-page":"4432","DOI":"10.1038\/s41467-023-39797-4","article-title":"Global air pollution exposure and poverty","volume":"14","author":"J Rentschler","year":"2023","journal-title":"Nat Commun"},{"key":"pone.0307514.ref038","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12950-015-0092-1","article-title":"Is air pollution a risk factor for rheumatoid arthritis?","volume":"12","author":"M Essouma","year":"2015","journal-title":"J Inflamm (Lond)"},{"key":"pone.0307514.ref039","doi-asserted-by":"crossref","first-page":"e0226738","DOI":"10.1371\/journal.pone.0226738","article-title":"Household air pollution and arthritis in low-and middle-income countries: Cross-sectional evidence from the World Health Organization\u2019s study on Global Ageing and Adult Health","volume":"14","author":"SS Yamamoto","year":"2019","journal-title":"PLoS One"},{"key":"pone.0307514.ref040","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/ar2751","article-title":"Rheumatoid arthritis and smoking: putting the pieces together","volume":"11","author":"Z Baka","year":"2009","journal-title":"Arthritis Res Ther"},{"issue":"23","key":"pone.0307514.ref041","doi-asserted-by":"crossref","first-page":"7179","DOI":"10.3390\/jcm11237179","article-title":"Lifestyle Factors and Their Influence on Rheumatoid Arthritis: A Narrative Review","volume":"11","author":"C Sch\u00e4fer","year":"2022","journal-title":"J Clin Med"},{"issue":"1","key":"pone.0307514.ref042","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12940-017-0285-6","article-title":"Genetic and epigenetic susceptibility of airway inflammation to PM2.5 in school children: new insights from quantile regression","volume":"16","author":"Y Zhang","year":"2017","journal-title":"Environ Health"},{"key":"pone.0307514.ref043","doi-asserted-by":"crossref","first-page":"105126","DOI":"10.1016\/j.ebiom.2024.105126","article-title":"Impact of ambient air pollution on colorectal cancer risk and survival: insights from a prospective cohort and epigenetic Mendelian randomization study","volume":"103","author":"F Jiang","year":"2024","journal-title":"EBioMedicine"},{"key":"pone.0307514.ref044","doi-asserted-by":"crossref","first-page":"170621","DOI":"10.1016\/j.scitotenv.2024.170621","article-title":"The relationship between cooking fuel use and sex hormone levels: A cross-sectional study and Mendelian randomization study","volume":"918","author":"X Wu","year":"2024","journal-title":"Sci Total Environ"},{"issue":"3","key":"pone.0307514.ref045","doi-asserted-by":"crossref","first-page":"e0300066","DOI":"10.1371\/journal.pone.0300066","article-title":"Exploring the causal relationship between airborne particulate matter and ulcerative colitis: A two-sample mendelian randomization study","volume":"19","author":"C Fu","year":"2024","journal-title":"PLoS One"},{"key":"pone.0307514.ref046","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1513\/pats.200701-031AW","article-title":"Gene-air pollution interactions in asthma","volume":"4","author":"SJ London","year":"2007","journal-title":"Proc Am Thorac Soc"},{"key":"pone.0307514.ref047","first-page":"428","article-title":"Genetic susceptibility to the respiratory effects of air pollution","volume":"85","author":"IA Yang","year":"2009","journal-title":"Postgrad Med J"},{"key":"pone.0307514.ref048","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1183\/09031936.06.00114905","article-title":"GSTM1 and GSTP1 and respiratory health in asthmatic children exposed to ozone","volume":"28","author":"I Romieu","year":"2006","journal-title":"Eur Respir J"},{"key":"pone.0307514.ref049","doi-asserted-by":"crossref","first-page":"52s","DOI":"10.1183\/09031936.03.00403003","article-title":"Genetic aspects of susceptibility to air pollution","volume":"40","author":"SR Kleeberger","year":"2003","journal-title":"Eur Respir J Suppl"},{"key":"pone.0307514.ref050","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1164\/rccm.200311-1499OC","article-title":"The role of Toll-like receptor 4 in environmental airway injury in mice","volume":"170","author":"JW Hollingsworth","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0307514.ref051","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1749-6632.2012.06605.x","article-title":"Cigarette smoke and ozone effect on murine inflammatory responses","volume":"1259","author":"C Gardi","year":"2012","journal-title":"Ann N Y Acad Sci"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0307514","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T17:24:21Z","timestamp":1727198661000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0307514"}},"subtitle":[],"editor":[{"given":"Worradorn","family":"Phairuang","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,9,24]]},"references-count":51,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0307514","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2024,9,24]]}}}