{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:35:43Z","timestamp":1792611343251,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T00:00:00Z","timestamp":1689120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50\u2010AR\u2010060772"],"award-info":[{"award-number":["P50\u2010AR\u2010060772"]}],"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":["R01\u2010AR\u2010065944"],"award-info":[{"award-number":["R01\u2010AR\u2010065944"]}],"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":["K99\u2010AR\u2010080243"],"award-info":[{"award-number":["K99\u2010AR\u2010080243"]}],"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"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To prospectively investigate population\u2010based metabolomics for incident gout and reproduce the findings for recurrent flares, accounting for serum urate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prediagnostic metabolome\u2010wide analysis among 105,615 UK Biobank participants with nuclear magnetic resonance metabolomic profiling data (168 total metabolites) from baseline blood samples collected 2006\u20132010 in those without history of gout. We calculated hazard ratios (HRs) for incident gout, adjusted for gout risk factors, excluding and including serum urate levels, overall and according to fasting duration before sample collection. Potential causal effects were tested with 2\u2010sample Mendelian randomization. Poisson regression was used to calculate rate ratios (RRs) for the association with recurrent flares among incident gout cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Correcting for multiple testing, 88 metabolites were associated with risk of incident gout (N\u00a0=\u00a01,303 cases) before serum urate adjustment, including glutamine and glycine (inversely), and lipids, branched\u2010chain amino acids, and most prominently, glycoprotein acetyls (GlycA;\n                      <jats:italic>P<\/jats:italic>\n                      =\u20099.17 \u00d7\u200910\n                      <jats:sup>\u221232<\/jats:sup>\n                      ). Only GlycA remained associated with incident gout following urate adjustment (HR 1.52 [95% confidence interval (95% CI) 1.22\u20131.88] between extreme quintiles); the HR increased progressively with fasting duration before sample collection, reaching 4.01 (95% CI 1.36\u201311.82) for \u22658 hours of fasting. Corresponding HRs per SD change in GlycA levels were 1.10 (95% CI 1.04\u20131.17) overall and 1.54 (95% CI 1.21\u20131.96) for \u22658 hours of fasting. GlycA levels were also associated with recurrent gout flares among incident gout cases (RR 1.90 [95% CI 1.27\u20132.85] between extreme quintiles) with larger associations with fasting. Mendelian randomization corroborated a potential causal role for GlycA on gout risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This prospective, population\u2010based study implicates GlycA, a stable long\u2010term biomarker reflecting neutrophil overactivity, in incident and recurrent gout flares (central manifestation from neutrophilic synovitis) beyond serum urate.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42523-toc-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42523","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T11:45:02Z","timestamp":1681299902000},"page":"1648-1657","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Prediagnostic Glycoprotein Acetyl Levels and Incident and Recurrent Flare Risk Accounting for Serum Urate Levels: A\n                    <scp>Population\u2010Based<\/scp>\n                    , Prospective Study and Mendelian Randomization Analysis"],"prefix":"10.1002","volume":"75","author":[{"given":"Amit D.","family":"Joshi","sequence":"first","affiliation":[{"name":"Clinical and Translational Epidemiology Unit, Department of Medicine Massachusetts General Hospital  Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4147-8348","authenticated-orcid":false,"given":"Natalie","family":"McCormick","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, and The Mongan Institute, Department of Medicine, Massachusetts General Hospital, Boston, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, and Arthritis Research Canada  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7557-3303","authenticated-orcid":false,"given":"Chio","family":"Yokose","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, and The Mongan Institute, Department of Medicine, Massachusetts General Hospital, Boston, and Department of Medicine Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health The University of Texas Health Science Center at Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4207-5866","authenticated-orcid":false,"given":"Adrienne","family":"Tin","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Mississippi Medical Center  Jackson"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Terkeltaub","sequence":"additional","affiliation":[{"name":"San Diego VA Healthcare Service and University of California San Diego  La Jolla California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0844-8726","authenticated-orcid":false,"given":"Tony R.","family":"Merriman","sequence":"additional","affiliation":[{"name":"Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, and Department of Biochemistry University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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