{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:32:50Z","timestamp":1793104370047,"version":"4.5.0"},"reference-count":69,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100022963","name":"Key Research and Development Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2020C03002"],"award-info":[{"award-number":["2020C03002"]}],"id":[{"id":"10.13039\/100022963","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":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the genetic architecture of low\u2010frequency and rare variants of serum urate (SU) in East Asian populations, and to clarify its role as a heritable and modifiable risk factor for gout and cardiometabolic diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted the largest two\u2010stage, whole\u2010genome sequencing\u2013based, genome\u2010wide scan for SU levels in East Asians, analyzing 9.1 million variants across 7,339 Han Chinese participants from the Healthy Zhejiang One Million People (HOPE) cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We verified associations at common and low\u2010frequency loci and identified a novel, replicable male\u2010specific locus at\n                      <jats:italic>MAN1A2<\/jats:italic>\n                      , along with a candidate low\u2010frequency male\u2010specific locus at\n                      <jats:italic>CPE<\/jats:italic>\n                      . Furthermore, using the STAARpipeline framework, we probed rare missense and putative loss\u2010of\u2010function variant aggregates in genes such as\n                      <jats:italic>SLC22A12<\/jats:italic>\n                      ,\n                      <jats:italic>SLC2A9<\/jats:italic>\n                      , and\n                      <jats:italic>G6PC2<\/jats:italic>\n                      , which were validated in our replication data set or the UK Biobank. Moreover, we identified and replicated novel associations with rare promoter variants near\n                      <jats:italic>HDC<\/jats:italic>\n                      and\n                      <jats:italic>SLC22A12<\/jats:italic>\n                      , highlighting their potential role in the context of noncoding regulation. Additionally, deep learning\u2013based fine\u2010mapping revealed transcription factors such as HNF1A, RUNX1, and SRF as potential up\u2010regulators of SU\u2010associated genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>By resolving East Asian\u2013specific allelic architecture and revealing ancestral diversity in SU genetics, this study advanced translational opportunities for precision urate\u2010lowering therapies and prioritized novel candidates for future research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70150","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T11:05:17Z","timestamp":1774350317000},"page":"2351-2364","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of Novel Noncoding Genetic Variants of Serum Urate Using Whole\u2010Genome Sequencing in 7,339 Chinese Participants"],"prefix":"10.1002","volume":"78","author":[{"given":"Qilong","family":"Tan","sequence":"first","affiliation":[{"name":"Center of Clinical Big Data and Analytics of the Second Affiliated Hospital and School of Public Health Zhejiang University School of Medicine  Hangzhou China"},{"name":"Zhejiang Key Laboratory of Intelligent Preventive Medicine  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center of Clinical Big Data and Analytics of the Second Affiliated Hospital and School of Public Health Zhejiang University School of Medicine  Hangzhou China"},{"name":"Zhejiang Key Laboratory of Intelligent Preventive Medicine  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlin","family":"Jia","sequence":"additional","affiliation":[{"name":"Center of Clinical Big Data and 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