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The aim of this study was to comprehensively describe the biologic characteristics (including genetic background) of clinically defined hyperuricemia subtypes in two large geographically independent gout cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Hyperuricemia subtype was defined as renal uric acid overload (ROL), renal uric acid underexcretion (RUE), combined, or renal normal. Twenty single nucleotide polymorphisms (SNPs) previously identified as gout risk loci or associated with serum urate (SU) concentration in the East Asian population were genotyped. Weighted polygenic risk scores were calculated to assess the cumulative effect of genetic risks on the subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 4,873 participants, 8.8% had an ROL subtype, 60.9% RUE subtype, 23.1% combined subtype, and 7.2% normal subtype. The ROL subtype was independently associated with older age at onset, lower SU, tophi, and diabetes mellitus; RUE was associated with lower body mass index (BMI) and non\u2013diabetes mellitus; the combined subtype was associated with younger age at onset, higher BMI, SU, estimated glomerular filtration rate (eGFR), and smoking; and the normal subtype was independently associated with older age at onset, lower SU, and eGFR. Thirteen SNPs were associated with gout with 6 shared loci and subtype\u2010dependent risk loci patterns. High polygenic risk scores were associated with ROL subtype (odds ratio [OR] = 9.63, 95% confidence interval [95% CI] 4.53\u201315.12), RUE subtype (OR = 2.18, 95% CI 1.57\u20133.03), and combined subtype (OR = 6.32, 95% CI 4.22\u20139.48) compared with low polygenic risk scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hyperuricemia subtypes classified according to renal uric acid handling have subtype\u2010specific clinical and genetic features, suggesting subtype\u2010unique pathophysiologic mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42838","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T18:25:20Z","timestamp":1709058320000},"page":"1130-1140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Hyperuricemia Subtypes Classified According to Renal Uric Acid Handling Manifesting Distinct Phenotypic and Genetic Profiles in People With Gout"],"prefix":"10.1002","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0720-2305","authenticated-orcid":false,"given":"Han","family":"Qi","sequence":"first","affiliation":[{"name":"The Affiliated Hospital of Qingdao University, Qingdao University, and Shandong Provincial Clinical Research Center for Immune Diseases and Gout  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingshu","family":"Sun","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5368-7473","authenticated-orcid":false,"given":"Robert","family":"Terkeltaub","sequence":"additional","affiliation":[{"name":"University of California San Diego"}],"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":"Qingdao University, Qingdao, China, and University of Alabama Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2259-5522","authenticated-orcid":false,"given":"Haibing","family":"Chen","sequence":"additional","affiliation":[{"name":"Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3726-6844","authenticated-orcid":false,"given":"Aichang","family":"Ji","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao 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