{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T10:45:09Z","timestamp":1791801909438,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006315","name":"ReumaNederland","doi-asserted-by":"publisher","award":["LLP\u201034"],"award-info":[{"award-number":["LLP\u201034"]}],"id":[{"id":"10.13039\/501100006315","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR075356"],"award-info":[{"award-number":["R01 AR075356"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG018820"],"award-info":[{"award-number":["U01 AG018820"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG018832"],"award-info":[{"award-number":["U01 AG018832"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG018947"],"award-info":[{"award-number":["U01 AG018947"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG019069"],"award-info":[{"award-number":["U01 AG019069"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AG076471"],"award-info":[{"award-number":["U19 AG076471"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Chondrocalcinosis, characterized by calcium crystal deposition within articular cartilage, affects 5% to 15% of the general population and has recently been identified as an osteoarthritis risk factor. However, its biologic pathways remain unclear. We conducted a genome\u2010wide association study (GWAS) of radiographically defined chondrocalcinosis knee and hand to identify its genetic determinants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>GWAS analyses of knee, hand, and combined chondrocalcinosis included up to 9,317 Rotterdam Study participants, with replication in the Versus Arthritis Osteoarthritis Genetics study and the Multicenter Osteoarthritis Study. Translational annotation prioritized effector genes. Associations between circulating thyroid\u2010stimulating hormone (TSH) and knee chondrocalcinosis were evaluated in the Rotterdam Study (n\u00a0=\u00a02,892).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified two genome\u2010wide significant loci for knee chondrocalcinosis: a novel signal (rs62424495) at the\n                      <jats:italic>ENPP1\u2010locus<\/jats:italic>\n                      (\u03b2\u00a0=\u00a0\u22120.21,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a02.6\u2009\u00d7\u200910\n                      <jats:sup>\u22129<\/jats:sup>\n                      ) and a previously reported signal (rs6927663) at the\n                      <jats:italic>RNF144B\u2010locus<\/jats:italic>\n                      (\u03b2\u00a0=\u00a00.12,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a08.8\u2009\u00d7\u200910\n                      <jats:sup>\u221210<\/jats:sup>\n                      ). Translational genomic analyses prioritized\n                      <jats:italic>ENPP1<\/jats:italic>\n                      and\n                      <jats:italic>RNF144B<\/jats:italic>\n                      as candidate effector genes, with evidence indicating that the chondrocalcinosis variant likely affects\n                      <jats:italic>RNF144B<\/jats:italic>\n                      regulation in thyroid tissue. The lead variant colocalized with circulating TSH levels (\u03b2\u00a0=\u00a00.027,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a02\u2009\u00d7\u200910\n                      <jats:sup>\u221214<\/jats:sup>\n                      ). Population analysis found that higher TSH levels were cross\u2010sectionally associated with presence and severity of knee chondrocalcinosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings identify genetic loci for radiographic chondrocalcinosis and offer hypothesis\u2010generating evidence of thyroid\u2010related pathways in its susceptibility, providing insight into molecular mechanisms underlying joint mineralization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70302","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:43:58Z","timestamp":1787222638000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic and Population Analyses Implicate Thyroid\u2010Related Regulation of\n                    <scp>\n                      <i>RNF144B<\/i>\n                    <\/scp>\n                    in Chondrocalcinosis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5421-9022","authenticated-orcid":false,"given":"Yahong","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Epidemiology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-2124","authenticated-orcid":false,"given":"Yanning","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Epidemiology Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul C.","family":"Okoro","sequence":"additional","affiliation":[{"name":"Marcus Institute for Aging Research Hebrew SeniorLife  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirine","family":"Saafi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jard","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Epidemiology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin H. G.","family":"Oei","sequence":"additional","affiliation":[{"name":"Department of Radiology &amp; Nuclear Medicine Erasmus Medical Center  Rotterdam Zuid\u2010Holland the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sita","family":"Bierma\u2010Zeinstra","sequence":"additional","affiliation":[{"name":"Department of General Practice Erasmus MC, University Medical Center Rotterdam  Rotterdam the Netherlands"},{"name":"Department of Orthopedics &amp; Sports Medicine Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trudy","family":"Voortman","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2668-2447","authenticated-orcid":false,"given":"David","family":"Felson","sequence":"additional","affiliation":[{"name":"Department of Medicine Boston University School of Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce B. J.","family":"van Meurs","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Orthopedics &amp; Sports Medicine Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layal","family":"Chaker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Epidemiology Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5577-3674","authenticated-orcid":false,"given":"J. Mark","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health University of Sheffield  Sheffield United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-6334","authenticated-orcid":false,"given":"Michelle S.","family":"Yau","sequence":"additional","affiliation":[{"name":"Marcus Institute for Aging Research Hebrew SeniorLife  Boston Massachusetts"},{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Bertrand","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Otto\u2010von\u2010Guericke\u2010University Magdeburg  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy G.","family":"Boer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.45.7.603"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(24)00122-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ard.2025.07.009"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23208"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.6.513"},{"issue":"6","key":"e_1_2_8_7_1","first-page":"981","article-title":"Prevalence of chondrocalcinosis in Italian subjects from northeastern Italy. The Pro.V.A. (PROgetto Veneto Anziani) study","volume":"27","author":"Ramonda R","year":"2009","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-025-00594-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.12.013"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.12.2431"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(75)90463-5"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/32.3.197"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-022-00875-4"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2024.10.017"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-022-00749-1"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-017-1565-6"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/343054"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.01.006"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ard.2025.04.002"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08494"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.071"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq340"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2213"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08771-z"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv402"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1070"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0538-0"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btad062"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1249"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21593-7"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz1776"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1078"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19356"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1151"},{"key":"e_1_2_8_36_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42284-5"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-17-0145"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33779-z"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224945"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.1.60"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0028"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.03.021"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0137-z"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbaa442"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy163"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-017-0370-3"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/00125480-200007020-00007"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.7860\/JCDR\/2015\/14640.6806"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6757154"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn082"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.133660"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ16-0534"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70302","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.70302","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70302","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T09:51:37Z","timestamp":1791798697000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.70302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,12]]},"references-count":52,"alternative-id":["10.1002\/art.70302"],"URL":"https:\/\/doi.org\/10.1002\/art.70302","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,12]]},"assertion":[{"value":"2026-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"art.70302"}}