{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T07:45:20Z","timestamp":1782632720101,"version":"3.54.5"},"reference-count":59,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Int Med Res"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Arthritis, including rheumatoid arthritis, gonarthrosis, and gouty arthritis, poses a substantial public health challenge. Regulatory T cells are critical for immune homeostasis, and their dysfunction contributes to arthritis pathogenesis; however, the specific gene regulatory programs causally influencing disease susceptibility remain elusive. We aimed to identify regulatory T cell\u2013specific therapeutic targets using single-cell cis-expression quantitative trait locus and Mendelian randomization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated single-cell regulatory T cell cis-expression quantitative trait locus data with genome-wide association study results from FinnGen R12 (16,314 rheumatoid arthritis, 61,356 gonarthrosis, and 12,342 gouty arthritis cases). Two-sample Mendelian randomization was employed to infer causality, using the inverse-variance weighted method, with rigorous sensitivity analyses conducted to ensure robustness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The analysis revealed distinct causal associations. In rheumatoid arthritis, upregulation of DexD\/H-box helicase 60 like (\n                      <jats:italic toggle=\"yes\">DDX60L)<\/jats:italic>\n                      significantly increased the disease risk (odds ratio = 2.10), whereas\n                      <jats:italic toggle=\"yes\">OAS1<\/jats:italic>\n                      expression served as a protective factor (odds ratio = 0.65). For gonarthrosis,\n                      <jats:italic toggle=\"yes\">OAS1<\/jats:italic>\n                      again demonstrated a protective effect (odds ratio = 0.897), whereas janus kinase and microtubule interacting protein 2 (\n                      <jats:italic toggle=\"yes\">JAKMIP2)<\/jats:italic>\n                      was identified as a modest risk factor (odds ratio = 1.019). Conversely, no significant regulatory T cell\u2013specific causal signals were observed for gouty arthritis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">OAS1<\/jats:italic>\n                      is a cross-disease regulatory T cell protector, whereas\n                      <jats:italic toggle=\"yes\">DDX60L<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">JAKMIP2<\/jats:italic>\n                      are disease-specific risk amplifiers. Engineering high-OAS1\/low-DDX60L\/low-JAKMIP2 regulatory T cells offers a genetically grounded blueprint for rheumatoid arthritis and gonarthrosis but not for gouty arthritis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03000605261459935","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:38:08Z","timestamp":1782369488000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integration of single-cell cis-expression quantitative trait locus and Mendelian randomization analyses identifies a Treg-specific gene for precision therapy in rheumatoid arthritis, gonarthrosis, and gouty arthritis"],"prefix":"10.1177","volume":"54","author":[{"given":"Tianqi","family":"Ren","sequence":"first","affiliation":[{"name":"Heilongjiang University of Chinese Medicine"},{"name":"The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3286-2118","authenticated-orcid":false,"given":"Yiwei","family":"Shen","sequence":"additional","affiliation":[{"name":"Binhai New Area Hospital of TCM. Tianjin (Fourth Teaching Hospital of Tianjin University of TCM)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Li","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine"},{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine"},{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelin","family":"Liu","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine"},{"name":"The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Bao","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine"},{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Li","sequence":"additional","affiliation":[{"name":"Shanhe YiPa Research Institute (Medical and Pharmaceutical Research Center), China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102241"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101981"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2023.100655"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-01037-w"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01525-8"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2103726"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-025-01305-x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.7326\/ANNALS-24-01249"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/jebm.12627"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1591369"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1671548"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms251910853"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/acr.25117"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114624"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/bjd\/ljae472"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26115421"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1511671"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1387975"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2025.04.003"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.626193"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1675114"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2022.05.005"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02359"},{"key":"e_1_3_3_25_2","article-title":"Mendelian randomization","volume":"12","author":"Birney E","year":"2022","unstructured":"Birney E. 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