{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:59:31Z","timestamp":1773147571358,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023QH397"],"award-info":[{"award-number":["ZR2023QH397"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background and Objectives<\/jats:title>\n Rheumatoid arthritis (RA) is a systemic autoimmune disease that is often complicated by interstitial lung disease (ILD), one of its most severe extra\u2010articular manifestations. However, whether RA causally contributes to ILD development remains unclear.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a two\u2010sample Mendelian randomization (MR) analysis to investigate whether RA has a causal effect on ILD. MR uses genetic variants associated with RA as instrumental variables to infer causality and minimize confounding. Genetic instruments for RA were obtained from a large European GWAS (ebi\u2010a\u2010GCST002318; 14,361 cases and 42,923 controls). The ILD outcome data were derived from FinnGen (finn\u2010b\u2010ILD, 1969 ILD cases and 196,986 controls), and autoimmune\u2010related codes were explicitly excluded to minimize phenotypic overlap. MR analyses were performed using inverse variance weighting (IVW), MR\u2010Egger regression, weighted median, mode\u2010based methods, and MR\u2010PRESSO to assess causality, heterogeneity, and pleiotropy.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The MR analysis identified 52 RA\u2010related single nucleotide polymorphisms (SNPs) (\n p<\/jats:italic>\n \u2009<\u20095\u2009\u00d7\u200910\n \u22128<\/jats:sup>\n ), which were selected as instrumental variables. The IVW method revealed a significant causal effect of RA on ILD risk, with an odds ratio (OR) of 1.155 (95% confidence interval [CI]: 1.083\u20131.232,\n p<\/jats:italic>\n \u2009=\u20091.04E\u201005). Directionally consistent results were obtained from weighted median and mode\u2010based methods. The MR\u2010Egger regression showed no evidence of directional pleiotropy (intercept\u2009=\u20090.014,\n p<\/jats:italic>\n \u2009=\u20090.147), and Cochran's Q test detected no significant heterogeneity (IVW Q\u2009=\u200945.424,\n p<\/jats:italic>\n \u2009=\u20090.694). Furthermore, the MR\u2010PRESSO global test did not detect horizontal pleiotropy (\n p<\/jats:italic>\n \u2009=\u20090.26), and no outlier SNPs were identified. Leave\u2010one\u2010out analysis indicated that no single SNP disproportionately influenced the overall estimate. The funnel plot showed a symmetrical distribution, suggesting no evidence of directional pleiotropy or influential bias.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This MR study provides robust genetic evidence supporting a potential causal relationship between RA and increased risk of ILD. These findings highlight the need for increased clinical vigilance, including early respiratory screening and monitoring in RA patients\u2014particularly those at high risk\u2014to facilitate timely detection and management of ILD.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/resp.70156","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T09:09:16Z","timestamp":1761901756000},"page":"162-173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mendelian Randomization Analysis of the Causal Link Between Rheumatoid Arthritis and Interstitial Lung Disease"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3314-1307","authenticated-orcid":false,"given":"Mengyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Laboratory of Basic Medical Sciences Qilu Hospital of Shandong University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Tai'an City Central Hospital Tai'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Laboratory of Basic Medical Sciences Qilu Hospital of Shandong University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Laboratory of Basic Medical Sciences Qilu Hospital of Shandong University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunhong","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Laboratory of Basic Medical Sciences Qilu Hospital of Shandong University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9538-7601","authenticated-orcid":false,"given":"Yiqing","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Laboratory of Basic Medical Sciences Qilu Hospital of Shandong University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.165.2.ats01"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2009-040GL"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-211468"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02776-2021"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/17476348.2024.2329612"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.12669\/pjms.36.3.1046"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01052-2"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0076-2018"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0011-2021"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-020-05320-z"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2022.11.035"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-024-01155-8"},{"key":"e_1_2_10_14_1","first-page":"21","article-title":"Rheumatoid Arthritis\u2010Associated Interstitial Lung Disease","volume":"4","author":"Solomon J. 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