{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T16:48:26Z","timestamp":1765039706165,"version":"build-2065373602"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea grant funded by Korea government","award":["NRF-2022R1F1A1068307"],"award-info":[{"award-number":["NRF-2022R1F1A1068307"]}]},{"name":"National Research Foundation of Korea grant funded by Korea government","award":["NRF-2019R1F1A1062965"],"award-info":[{"award-number":["NRF-2019R1F1A1062965"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Gout\u2014a very painful inflammatory arthritis caused by the deposition of monosodium urate crystals in the joints\u2014is influenced by several factors. We identified the association of single- nucleotide polymorphisms (SNPs) that link gout with health-related lifestyle factors using genomic data from the Korean Genome and Epidemiology Study. We conducted a genome-wide association study (GWAS) on 18,927 samples of 438 Korean patients with gout and 18,489 controls for the discovery stage. For the replication stage, another batch containing samples of 326 patients with gout and 2,737 controls were analyzed. Lastly, a meta-analysis was performed using these two cohorts. We analyzed the effects of health-related lifestyle factors, including eating habits, physical activity, drinking behavior, and smoking behavior, on gout. After identifying the association between GWAS-derived SNPs and health-related lifestyle factors, we confirmed the interaction between the polygenic risk score (PRS) and health-related lifestyle factors. We identified 15 SNPs related to gout, among which rs1481012 of <jats:italic>ABCG2<\/jats:italic> located on chromosome 4 has been newly discovered (<jats:italic>P<\/jats:italic> = 2.46e<jats:sup>-11<\/jats:sup>). On examining the interaction between SNPs and health-related lifestyles, rs3109823\u2014located in <jats:italic>ABCG2<\/jats:italic>\u2014was found to be associated with smoking status. In addition, rs11936395\u2014located in <jats:italic>SLC2A9<\/jats:italic>\u2014was significantly associated with the average momentum of exercise per session, whereas rs11066325 located in <jats:italic>PTPN11<\/jats:italic>, showed a significant association with the number of exercise sessions per week, smoking status, drinking status, and amount of soju drink per session. rs9421589\u2014located in <jats:italic>FAM35A<\/jats:italic>\u2014was significantly associated with the duration of smoking. In addition, we verified that the association between PRS and duration of smoking affects gout. Thus, in this study, we identified novel SNPs that link gout with health-related lifestyle factors in the Korean population.<\/jats:p>","DOI":"10.1371\/journal.pone.0295038","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T18:34:07Z","timestamp":1701974047000},"page":"e0295038","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Single-nucleotide polymorphisms link gout with health-related lifestyle factors in Korean cohorts"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3164-1436","authenticated-orcid":true,"given":"Hye Kyung","family":"Jeon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9971-9036","authenticated-orcid":true,"given":"Hae Young","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,12,7]]},"reference":[{"key":"pone.0295038.ref001","doi-asserted-by":"crossref","first-page":"54","DOI":"10.7861\/clinmedicine.17-1-54","article-title":"Gout\u2013a guide for the general and acute physicians.","volume":"17","author":"A Abhishek","year":"2017","journal-title":"Clin Med"},{"key":"pone.0295038.ref002","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.semnephrol.2004.09.002","article-title":"Uric acid, evolution and primitive cultures","volume":"25","author":"RJ Johnson","year":"2005","journal-title":"Semin Nephrol"},{"key":"pone.0295038.ref003","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.maturitas.2018.10.012","article-title":"Gout\u2013An update of aetiology, genetics, co-morbidities and management","volume":"118","author":"PC Robinson","year":"2018","journal-title":"Maturitas."},{"key":"pone.0295038.ref004","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.rdc.2014.07.002","article-title":"Gout: A review of nonmodifiable and modifiable risk factors.","volume":"40","author":"LA MacFarlane","year":"2018","journal-title":"Rheum Dis Clin North Am"},{"key":"pone.0295038.ref005","first-page":"157","article-title":"Epistatic interaction between PKD2 and ABCG2 influences the pathogenesis of hyperuricemia and gout","author":"Z Dong","year":"2020","journal-title":"Hereditas"},{"key":"pone.0295038.ref006","doi-asserted-by":"crossref","first-page":"913","DOI":"10.3904\/kjim.2015.30.6.913","article-title":"Genetic analysis of ABCG2 and SLC2A9 gene polymorphisms in gouty arthritis in a Korean population","volume":"30","author":"YS Kim","year":"2015","journal-title":"Korean J Intern Med"},{"key":"pone.0295038.ref007","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1136\/annrheumdis-2016-209632","article-title":"GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes","volume":"76","author":"A Nakayama","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"pone.0295038.ref008","doi-asserted-by":"crossref","first-page":"80","DOI":"10.5114\/ceji.2020.94702","article-title":"Genetic association of polymorphism rs2230054 in CXCR2 gene with gout in Chinese Han male population","volume":"45","author":"Y Wang","year":"2020","journal-title":"Cent Eur J Immunol"},{"key":"pone.0295038.ref009","doi-asserted-by":"crossref","first-page":"e00291","DOI":"10.1002\/prp2.291","article-title":"Uricosuric targets of tranilast","volume":"5","author":"AK Mandal","year":"2017","journal-title":"Pharmacol Res Perspect"},{"key":"pone.0295038.ref010","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev-physiol-021113-170343","article-title":"The molecular physiology of uric acid homeostasis","volume":"77","author":"AK Mandal","year":"2015","journal-title":"Annu Rev Physiol"},{"key":"pone.0295038.ref011","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/jhg.2012.39","article-title":"Genetic architecture for susceptibility to gout in the KARE cohort study","volume":"57","author":"J Shin","year":"2012","journal-title":"J Hum Genet"},{"key":"pone.0295038.ref012","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00296-011-2303-2","article-title":"Effects of SLC2A9 variants on uric acid levels in a Korean population.","volume":"33","author":"JW Sull","year":"2013","journal-title":"Rheumatol Int."},{"key":"pone.0295038.ref013","article-title":"Genome-wide association study for hyperuricemia in a community-based Korean cohort.","author":"CN Son","year":"2016","journal-title":"Doctoral dissertation. 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