{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T16:58:09Z","timestamp":1788195489726,"version":"build-2803163510"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T00:00:00Z","timestamp":1498089600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T00:00:00Z","timestamp":1498089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Gout is a chronic disease resulting from elevated serum urate (SU). Previous genome-wide association studies (GWAS) have identified dozens of susceptibility loci for SU\/gout, but few have been conducted for Chinese descent. Here, we try to extensively investigate whether these loci contribute to gout risk in Han Chinese. A total of 2255 variants in linkage disequilibrium (LD) with GWAS identified SU\/gout associated variants were analyzed in a Han Chinese cohort of 1255 gout patients and 1848 controls. Cumulative genetic risk score analysis was performed to assess the cumulative effect of multiple \u201crisk\u201d variants on gout incidence. 23 variants (41%) of LD pruned variants set (n\u2009=\u200956) showed nominal association with gout in our sample (p\u2009&lt;\u20090.05). Some of the previously reported gout associated loci (except\n                    <jats:italic>ALDH16A1<\/jats:italic>\n                    ), including\n                    <jats:italic>ABCG2<\/jats:italic>\n                    ,\n                    <jats:italic>SLC2A9<\/jats:italic>\n                    ,\n                    <jats:italic>GCKR<\/jats:italic>\n                    ,\n                    <jats:italic>ALDH2<\/jats:italic>\n                    and\n                    <jats:italic>CNIH2<\/jats:italic>\n                    , were replicated. Cumulative genetic risk score analyses showed that the risk of gout increased for individuals with the growing number (\u22658) of the risk alleles on gout associated loci. Most of the gout associated loci identified in previous GWAS were confirmed in an independent Chinese cohort, and the SU associated loci also confer susceptibility to gout. These findings provide important information of the genetic association of gout.\n                  <\/jats:p>","DOI":"10.1038\/s41598-017-04127-4","type":"journal-article","created":{"date-parts":[[2017,6,16]],"date-time":"2017-06-16T10:18:37Z","timestamp":1497608317000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Replication of Gout\/Urate Concentrations GWAS Susceptibility Loci Associated with Gout in a Han Chinese Population"],"prefix":"10.1038","volume":"7","author":[{"given":"Zhiqiang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaowei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dajiang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keke","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaotong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinde","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Sheng","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changgui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,22]]},"reference":[{"key":"4127_CR1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1017\/S0001566000006401","volume":"32","author":"JB Whitfield","year":"1983","unstructured":"Whitfield, J. B. & Martin, N. G. Inheritance and alcohol as factors influencing plasma uric acid levels. Acta geneticae medicae et gemellologiae \n                           32, 117\u2013126 (1983).","journal-title":"Acta geneticae medicae et gemellologiae"},{"key":"4127_CR2","doi-asserted-by":"publisher","first-page":"e194","DOI":"10.1371\/journal.pgen.0030194","volume":"3","author":"S Li","year":"2007","unstructured":"Li, S. et al. The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts. PLoS genetics \n                           3, e194, doi:10.1371\/journal.pgen.0030194 (2007).","journal-title":"PLoS genetics"},{"key":"4127_CR3","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1016\/S0140-6736(08)61343-4","volume":"372","author":"A Dehghan","year":"2008","unstructured":"Dehghan, A. et al. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet \n                           372, 1953\u20131961, doi:10.1016\/S0140-6736(08)61343-4 (2008).","journal-title":"Lancet"},{"key":"4127_CR4","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/ng.107","volume":"40","author":"A Doring","year":"2008","unstructured":"Doring, A. et al. SLC2A9 influences uric acid concentrations with pronounced sex-specific effects. Nature genetics \n                           40, 430\u2013436, doi:10.1038\/ng.107 (2008).","journal-title":"Nature genetics"},{"key":"4127_CR5","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/ng.106","volume":"40","author":"V Vitart","year":"2008","unstructured":"Vitart, V. et al. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nature genetics \n                           40, 437\u2013442, doi:10.1038\/ng.106 (2008).","journal-title":"Nature genetics"},{"key":"4127_CR6","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.ajhg.2007.11.001","volume":"82","author":"C Wallace","year":"2008","unstructured":"Wallace, C. et al. Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia. American journal of human genetics \n                           82, 139\u2013149, doi:10.1016\/j.ajhg.2007.11.001 (2008).","journal-title":"American journal of human genetics"},{"key":"4127_CR7","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/ng.531","volume":"42","author":"Y Kamatani","year":"2010","unstructured":"Kamatani, Y. et al. Genome-wide association study of hematological and biochemical traits in a Japanese population. Nature genetics \n                           42, 210\u2013215, doi:10.1038\/ng.531 (2010).","journal-title":"Nature genetics"},{"key":"4127_CR8","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1161\/CIRCGENETICS.109.934455","volume":"3","author":"Q Yang","year":"2010","unstructured":"Yang, Q. et al. Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors. Circulation. Cardiovascular genetics \n                           3, 523\u2013530, doi:10.1161\/CIRCGENETICS.109.934455 (2010).","journal-title":"Circulation. Cardiovascular genetics"},{"key":"4127_CR9","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1038\/ng.972","volume":"43","author":"P Sulem","year":"2011","unstructured":"Sulem, P. et al. Identification of low-frequency variants associated with gout and serum uric acid levels. Nature genetics \n                           43, 1127\u20131130, doi:10.1038\/ng.972 (2011).","journal-title":"Nature genetics"},{"key":"4127_CR10","doi-asserted-by":"publisher","first-page":"4056","DOI":"10.1093\/hmg\/ddr307","volume":"20","author":"A Tin","year":"2011","unstructured":"Tin, A. et al. Genome-wide association study for serum urate concentrations and gout among African Americans identifies genomic risk loci and a novel URAT1 loss-of-function allele. Human molecular genetics \n                           20, 4056\u20134068, doi:10.1093\/hmg\/ddr307 (2011).","journal-title":"Human molecular genetics"},{"key":"4127_CR11","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/ng.2500","volume":"45","author":"A Kottgen","year":"2013","unstructured":"Kottgen, A. et al. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nature genetics \n                           45, 145\u2013154, doi:10.1038\/ng.2500 (2013).","journal-title":"Nature genetics"},{"key":"4127_CR12","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1755-8794-7-10","volume":"7","author":"B Yang","year":"2014","unstructured":"Yang, B. et al. A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population. BMC medical genomics \n                           7, 10, doi:10.1186\/1755-8794-7-10 (2014).","journal-title":"BMC medical genomics"},{"key":"4127_CR13","doi-asserted-by":"publisher","first-page":"7041","DOI":"10.1038\/ncomms8041","volume":"6","author":"C Li","year":"2015","unstructured":"Li, C. et al. Genome-wide association analysis identifies three new risk loci for gout arthritis in Han Chinese. Nature communications \n                           6, 7041, doi:10.1038\/ncomms8041 (2015).","journal-title":"Nature communications"},{"key":"4127_CR14","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1136\/annrheumdis-2014-206191","volume":"75","author":"H Matsuo","year":"2016","unstructured":"Matsuo, H. et al. Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes. Annals of the rheumatic diseases \n                           75, 652\u2013659, doi:10.1136\/annrheumdis-2014-206191 (2016).","journal-title":"Annals of the rheumatic diseases"},{"key":"4127_CR15","doi-asserted-by":"publisher","first-page":"e1000504","DOI":"10.1371\/journal.pgen.1000504","volume":"5","author":"M Kolz","year":"2009","unstructured":"Kolz, M. et al. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS genetics \n                           5, e1000504, doi:10.1371\/journal.pgen.1000504 (2009).","journal-title":"PLoS genetics"},{"key":"4127_CR16","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1136\/ard.2009.113357","volume":"69","author":"HP Tu","year":"2010","unstructured":"Tu, H. P. et al. Associations of a non-synonymous variant in SLC2A9 with gouty arthritis and uric acid levels in Han Chinese subjects and Solomon Islanders. Annals of the rheumatic diseases \n                           69, 887\u2013890, doi:10.1136\/ard.2009.113357 (2010).","journal-title":"Annals of the rheumatic diseases"},{"key":"4127_CR17","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1136\/jmg.2009.068619","volume":"47","author":"C Li","year":"2010","unstructured":"Li, C. et al. Multiple single nucleotide polymorphisms in the human urate transporter 1 (hURAT1) gene are associated with hyperuricaemia in Han Chinese. Journal of medical genetics \n                           47, 204\u2013210, doi:10.1136\/jmg.2009.068619 (2010).","journal-title":"Journal of medical genetics"},{"key":"4127_CR18","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1007\/s00439-012-1151-9","volume":"131","author":"J Wang","year":"2012","unstructured":"Wang, J. et al. Association between gout and polymorphisms in GCKR in male Han Chinese. Human genetics \n                           131, 1261\u20131265, doi:10.1007\/s00439-012-1151-9 (2012).","journal-title":"Human genetics"},{"key":"4127_CR19","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s00439-009-0760-4","volume":"127","author":"B Wang","year":"2010","unstructured":"Wang, B. et al. Genetic analysis of ABCG2 gene C421A polymorphism with gout disease in Chinese Han male population. Human genetics \n                           127, 245\u2013246, doi:10.1007\/s00439-009-0760-4 (2010).","journal-title":"Human genetics"},{"key":"4127_CR20","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/art.38884","volume":"67","author":"T Chiba","year":"2015","unstructured":"Chiba, T. et al. NPT1\/SLC17A1 Is a Renal Urate Exporter in Humans and Its Common Gain-of-Function Variant Decreases the Risk of Renal Underexcretion Gout. Arthritis & Rheumatology \n                           67, 281\u2013287, doi:10.1002\/art.38884 (2015).","journal-title":"Arthritis & Rheumatology"},{"key":"4127_CR21","doi-asserted-by":"publisher","unstructured":"Matsuo, H. et al. Common Defects of ABCG2, a High-Capacity Urate Exporter, Cause Gout: A Function-Based Genetic Analysis in a Japanese Population. Science Translational Medicine \n                           1, doi:10.1126\/scitranslmed.3000237 (2009).","DOI":"10.1126\/scitranslmed.3000237"},{"key":"4127_CR22","doi-asserted-by":"publisher","unstructured":"Sakiyama, M. et al. Identification of rs671, a common variant of ALDH2, as a gout susceptibility locus. Scientific Reports \n                           6, doi:10.1038\/srep25360 (2016).","DOI":"10.1038\/srep25360"},{"key":"4127_CR23","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. The American Journal of Human Genetics \n                           81, 559\u2013575 (2007).","journal-title":"The American Journal of Human Genetics"},{"key":"4127_CR24","doi-asserted-by":"publisher","unstructured":"World Medical, A. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Jama \n                           310, 2191\u20132194, doi:10.1001\/jama.2013.281053 (2013).","DOI":"10.1001\/jama.2013.281053"},{"key":"4127_CR25","doi-asserted-by":"publisher","first-page":"10338","DOI":"10.1073\/pnas.0901249106","volume":"106","author":"OM Woodward","year":"2009","unstructured":"Woodward, O. M. et al. Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proceedings of the National Academy of Sciences of the United States of America \n                           106, 10338\u201310342, doi:10.1073\/pnas.0901249106 (2009).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-04127-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-04127-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-04127-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:49:34Z","timestamp":1671756574000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-04127-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,22]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["4127"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-04127-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,22]]},"assertion":[{"value":"31 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"4094"}}