{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T16:58:08Z","timestamp":1788195488967,"version":"build-2803163510"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hum Genet"],"published-print":{"date-parts":[[2016,9]]},"DOI":"10.1038\/jhg.2016.57","type":"journal-article","created":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T06:21:30Z","timestamp":1464243690000},"page":"803-810","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Additive composite ABCG2, SLC2A9 and SLC22A12 scores of high-risk alleles with alcohol use modulate gout risk"],"prefix":"10.1038","volume":"61","author":[{"given":"Hung-Pin","family":"Tu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Min","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Min-Shan Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Shin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Ming","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Hung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Ming","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiu-Shong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Chin","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,26]]},"reference":[{"key":"BFjhg201657_CR1","doi-asserted-by":"publisher","first-page":"3136","DOI":"10.1002\/art.30520","volume":"63","author":"Y Zhu","year":"2011","unstructured":"Zhu, Y., Pandya, B. J. & Choi, H. K. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 63, 3136\u20133141 (2011).","journal-title":"Arthritis Rheum."},{"key":"BFjhg201657_CR2","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1136\/annrheumdis-2013-204067","volume":"74","author":"CF Kuo","year":"2015","unstructured":"Kuo, C. F., Grainge, M. J., See, L. C., Yu, K. H., Luo, S. F., Valdes, A. M. et al. Familial aggregation of gout and relative genetic and environmental contributions: a nationwide population study in Taiwan. Ann. Rheum. Dis. 74, 369\u2013374 (2015).","journal-title":"Ann. Rheum. Dis."},{"key":"BFjhg201657_CR3","doi-asserted-by":"publisher","first-page":"499","DOI":"10.7326\/0003-4819-143-7-200510040-00009","volume":"143","author":"HK Choi","year":"2005","unstructured":"Choi, H. K., Mount, D. B. & Reginato, A. M. Pathogenesis of gout. Ann. Intern. Med. 143, 499\u2013516 (2005).","journal-title":"Ann. Intern. Med."},{"key":"BFjhg201657_CR4","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1016\/S0140-6736(08)61344-6","volume":"372","author":"M Aringer","year":"2008","unstructured":"Aringer, M. & Graessler, J. Understanding deficient elimination of uric acid. Lancet 372, 1929\u20131930 (2008).","journal-title":"Lancet"},{"key":"BFjhg201657_CR5","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/nrrheum.2009.236","volume":"6","author":"R Terkeltaub","year":"2010","unstructured":"Terkeltaub, R. Update on gout: new therapeutic strategies and options. Nat. Rev. Rheumatol. 6, 30\u201338 (2010).","journal-title":"Nat. Rev. Rheumatol."},{"key":"BFjhg201657_CR6","first-page":"125","volume":"20","author":"MA Hediger","year":"2005","unstructured":"Hediger, M. A., Johnson, R. J., Miyazaki, H. & Endou, H. Molecular physiology of urate transport. Physiology (Bethesda) 20, 125\u2013133 (2005).","journal-title":"Physiology (Bethesda)"},{"key":"BFjhg201657_CR7","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1681\/ASN.V1251001","volume":"12","author":"SJ Kelly","year":"2001","unstructured":"Kelly, S. J., Delnomdedieu, M., Oliverio, M. I., Williams, L. D., Saifer, M. G., Sherman, M. R. et al. Diabetes insipidus in uricase-deficient mice: a model for evaluating therapy with poly(ethylene glycol)-modified uricase. J. Am. Soc. Nephrol. 12, 1001\u20131009 (2001).","journal-title":"J. Am. Soc. Nephrol."},{"key":"BFjhg201657_CR8","doi-asserted-by":"publisher","first-page":"9412","DOI":"10.1073\/pnas.86.23.9412","volume":"86","author":"XW Wu","year":"1989","unstructured":"Wu, X. W., Lee, C. C., Muzny, D. M. & Caskey, C. T. Urate oxidase: primary structure and evolutionary implications. Proc. Natl Acad. Sci. USA 86, 9412\u20139416 (1989).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFjhg201657_CR9","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1007\/BF00163854","volume":"34","author":"XW Wu","year":"1992","unstructured":"Wu, X. W., Muzny, D. M., Lee, C. C. & Caskey, C. T. Two independent mutational events in the loss of urate oxidase during hominoid evolution. J. Mol. Evol. 34, 78\u201384 (1992).","journal-title":"J. Mol. Evol."},{"issue":"suppl. 1","key":"BFjhg201657_CR10","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1186\/ar1907","volume":"8","author":"KG Saag","year":"2006","unstructured":"Saag, K.G. & Choi, H. Epidemiology, risk factors, and lifestyle modifications for gout. Arthritis Res. Ther. 8 (suppl. 1), S2 (2006).","journal-title":"Arthritis Res. Ther."},{"key":"BFjhg201657_CR11","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1152\/physiolgenomics.00207.2007","volume":"33","author":"SA Eraly","year":"2008","unstructured":"Eraly, S. A., Vallon, V., Rieg, T., Gangoiti, J. A., Wikoff, W. R., Siuzdak, G. et al. Multiple organic anion transporters contribute to net renal excretion of uric acid. Physiol. Genomics 33, 180\u2013192 (2008).","journal-title":"Physiol. Genomics"},{"key":"BFjhg201657_CR12","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., Kottgen, A., Yang, Q., Hwang, S. J., Kao, W. L., Rivadeneira, F. et al. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet 372, 1953\u20131961 (2008).","journal-title":"Lancet"},{"key":"BFjhg201657_CR13","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/ng.106","volume":"40","author":"V Vitart","year":"2008","unstructured":"Vitart, V., Rudan, I., Hayward, C., Gray, N. K., Floyd, J., Palmer, C. N. et al. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat. Genet. 40, 437\u2013442 (2008).","journal-title":"Nat. Genet."},{"key":"BFjhg201657_CR14","doi-asserted-by":"publisher","first-page":"e1000504","DOI":"10.1371\/journal.pgen.1000504","volume":"5","author":"M Kolz","year":"2009","unstructured":"Kolz, M., Johnson, T., Sanna, S., Teumer, A., Vitart, V., Perola, M. et al. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet. 5, e1000504 (2009).","journal-title":"PLoS Genet."},{"key":"BFjhg201657_CR15","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1038\/ng.2352","volume":"44","author":"Y Okada","year":"2012","unstructured":"Okada, Y., Sim, X., Go, M. J., Wu, J. Y., Gu, D., Takeuchi, F. et al. Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations. Nat. Genet. 44, 904\u2013909 (2012).","journal-title":"Nat. Genet."},{"key":"BFjhg201657_CR16","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1038\/nrrheum.2012.144","volume":"8","author":"AM Reginato","year":"2012","unstructured":"Reginato, A. M., Mount, D. B., Yang, I. & Choi, H. K. The genetics of hyperuricaemia and gout. Nat. Rev. Rheumatol. 8, 610\u2013621 (2012).","journal-title":"Nat. Rev. Rheumatol."},{"key":"BFjhg201657_CR17","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.jbspin.2010.02.027","volume":"78","author":"TR Merriman","year":"2011","unstructured":"Merriman, T. R. & Dalbeth, N. The genetic basis of hyperuricaemia and gout. Joint Bone Spine 78, 35\u201340 (2011).","journal-title":"Joint Bone Spine"},{"key":"BFjhg201657_CR18","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1002\/art.1780200320","volume":"20","author":"SL Wallace","year":"1977","unstructured":"Wallace, S. L., Robinson, H., Masi, A. T., Decker, J. L., McCarty, D. J. & Yu, T. F. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 20, 895\u2013900 (1977).","journal-title":"Arthritis Rheum."},{"key":"BFjhg201657_CR19","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1093\/ije\/dyt028","volume":"42","author":"AM Ko","year":"2013","unstructured":"Ko, A. M., Tu, H. P., Liu, T. T., Chang, J. G., Yuo, C. Y., Chiang, S. L. et al. ALPK1 genetic regulation and risk in relation to gout. Int. J. Epidemiol. 42, 466\u2013474 (2013).","journal-title":"Int. J. Epidemiol."},{"key":"BFjhg201657_CR20","doi-asserted-by":"publisher","first-page":"749","DOI":"10.3899\/jrheum.130870","volume":"41","author":"HP Tu","year":"2014","unstructured":"Tu, H. P., Ko, A. M., Chiang, S. L., Lee, S. S., Lai, H. M., Chung, C. M. et al. Joint effects of alcohol consumption and ABCG2 Q141K on chronic tophaceous gout risk. J. Rheumatol. 41, 749\u2013758 (2014).","journal-title":"J. Rheumatol."},{"key":"BFjhg201657_CR21","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1136\/ard.2009.114504","volume":"69","author":"HP Tu","year":"2010","unstructured":"Tu, H. P., Chen, C. J., Lee, C. H., Tovosia, S., Ko, A. M., Wang, S. J. et al. The SLC22A12 gene is associated with gout in Han Chinese and Solomon Islanders. Ann. Rheum. Dis. 69, 1252\u20131254 (2010).","journal-title":"Ann. Rheum. Dis."},{"key":"BFjhg201657_CR22","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1136\/ard.2009.113357","volume":"69","author":"HP Tu","year":"2010","unstructured":"Tu, H. P., Chen, C. J., Tovosia, S., Ko, A. M., Lee, C. H., Ou, T. T. et al. Associations of a non-synonymous variant in SLC2A9 with gouty arthritis and uric acid levels in Han Chinese subjects and Solomon Islanders. Ann. Rheum. Dis. 69, 887\u2013890 (2010).","journal-title":"Ann. Rheum. Dis."},{"key":"BFjhg201657_CR23","doi-asserted-by":"publisher","first-page":"R220","DOI":"10.1186\/ar4417","volume":"15","author":"TJ Flynn","year":"2013","unstructured":"Flynn, T. J., Phipps-Green, A., Hollis-Moffatt, J. E., Merriman, M. E., Topless, R., Montgomery, G. et al. Association analysis of the SLC22A11 (organic anion transporter 4) and SLC22A12 (urate transporter 1) urate transporter locus with gout in New Zealand case-control sample sets reveals multiple ancestral-specific effects. Arthritis Res. Ther. 15, R220 (2013).","journal-title":"Arthritis Res. Ther."},{"key":"BFjhg201657_CR24","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1111\/j.1365-2125.2006.02655.x","volume":"62","author":"SV Vormfelde","year":"2006","unstructured":"Vormfelde, S. V., Schirmer, M., Hagos, Y., Toliat, M. R., Engelhardt, S., Meineke, I. et al. Torsemide renal clearance and genetic variation in luminal and basolateral organic anion transporters. Br. J. Clin. Pharmacol. 62, 323\u2013335 (2006).","journal-title":"Br. J. Clin. Pharmacol."},{"key":"BFjhg201657_CR25","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1161\/CIRCGENETICS.109.934455","volume":"3","author":"Q Yang","year":"2010","unstructured":"Yang, Q., Kottgen, A., Dehghan, A., Smith, A. V., Glazer, N. L., Chen, M. H. et al. Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors. Circ. Cardiovasc. Genet. 3, 523\u2013530 (2010).","journal-title":"Circ. Cardiovasc. Genet."},{"key":"BFjhg201657_CR26","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/ng.2500","volume":"45","author":"A Kottgen","year":"2013","unstructured":"Kottgen, A., Albrecht, E., Teumer, A., Vitart, V., Krumsiek, J., Hundertmark, C. et al. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat. Genet. 45, 145\u2013154 (2013).","journal-title":"Nat. Genet."},{"key":"BFjhg201657_CR27","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A., Bender, D. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559\u2013575 (2007).","journal-title":"Am. J. Hum. Genet."},{"key":"BFjhg201657_CR28","doi-asserted-by":"publisher","first-page":"823","DOI":"10.2217\/14622416.6.8.823","volume":"6","author":"MD Ritchie","year":"2005","unstructured":"Ritchie, M. D. & Motsinger, A. A. Multifactor dimensionality reduction for detecting gene-gene and gene-environment interactions in pharmacogenomics studies. Pharmacogenomics 6, 823\u2013834 (2005).","journal-title":"Pharmacogenomics"},{"key":"BFjhg201657_CR29","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1097\/00001648-199209000-00012","volume":"3","author":"DW Hosmer","year":"1992","unstructured":"Hosmer, D. W. & Lemeshow, S. Confidence interval estimation of interaction. Epidemiology 3, 452\u2013456 (1992).","journal-title":"Epidemiology"},{"key":"BFjhg201657_CR30","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s10654-005-7835-x","volume":"20","author":"T Andersson","year":"2005","unstructured":"Andersson, T., Alfredsson, L., Kallberg, H., Zdravkovic, S. & Ahlbom, A. Calculating measures of biological interaction. Eur. J. Epidemiol. 20, 575\u2013579 (2005).","journal-title":"Eur. J. Epidemiol."},{"key":"BFjhg201657_CR31","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1093\/aje\/153.10.1016","volume":"153","author":"LD Botto","year":"2001","unstructured":"Botto, L. D. & Khoury, M. J. Commentary: facing the challenge of gene-environment interaction: the two-by-four table and beyond. Am. J. Epidemiol. 153, 1016\u20131020 (2001).","journal-title":"Am. J. Epidemiol."},{"key":"BFjhg201657_CR32","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.addr.2008.11.003","volume":"61","author":"RW Robey","year":"2009","unstructured":"Robey, R. W., To, K. K., Polgar, O., Dohse, M., Fetsch, P., Dean, M. et al. ABCG2: a perspective. Adv. Drug Deliv. Rev. 61, 3\u201313 (2009).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"BFjhg201657_CR33","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/nature742","volume":"417","author":"A Enomoto","year":"2002","unstructured":"Enomoto, A., Kimura, H., Chairoungdua, A., Shigeta, Y., Jutabha, P., Cha, S. H. et al. Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature 417, 447\u2013452 (2002).","journal-title":"Nature"},{"key":"BFjhg201657_CR34","doi-asserted-by":"publisher","first-page":"R85","DOI":"10.1186\/ar3356","volume":"13","author":"JE Hollis-Moffatt","year":"2011","unstructured":"Hollis-Moffatt, J. E., Gow, P. J., Harrison, A. A., Highton, J., Jones, P. B., Stamp, L. K. et al. The SLC2A9 nonsynonymous Arg265His variant and gout: evidence for a population-specific effect on severity. Arthritis Res. Ther. 13, R85 (2011).","journal-title":"Arthritis Res. Ther."},{"key":"BFjhg201657_CR35","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.amjmed.2013.12.019","volume":"127","author":"T Neogi","year":"2014","unstructured":"Neogi, T., Chen, C., Niu, J., Chaisson, C., Hunter, D. J. & Zhang, Y. Alcohol quantity and type on risk of recurrent gout attacks: an internet-based case-crossover study. Am. J. Med. 127, 311\u2013318 (2014).","journal-title":"Am. J. Med."},{"key":"BFjhg201657_CR36","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1016\/S0140-6736(04)16000-5","volume":"363","author":"HK Choi","year":"2004","unstructured":"Choi, H. K., Atkinson, K., Karlson, E. W., Willett, W. & Curhan, G. Alcohol intake and risk of incident gout in men: a prospective study. Lancet 363, 1277\u20131281 (2004).","journal-title":"Lancet"},{"key":"BFjhg201657_CR37","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1056\/NEJM198212233072602","volume":"307","author":"J Faller","year":"1982","unstructured":"Faller, J. & Fox, I. H. Ethanol-induced hyperuricemia: evidence for increased urate production by activation of adenine nucleotide turnover. N. Engl. J. Med. 307, 1598\u20131602 (1982).","journal-title":"N. Engl. J. Med."},{"key":"BFjhg201657_CR38","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1093\/rheumatology\/ken460","volume":"48","author":"N Dalbeth","year":"2009","unstructured":"Dalbeth, N. & Merriman, T. Crystal ball gazing: new therapeutic targets for hyperuricaemia and gout. Rheumatology (Oxford) 48, 222\u2013226 (2009).","journal-title":"Rheumatology (Oxford)"},{"key":"BFjhg201657_CR39","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/0002-9343(87)90441-4","volume":"82","author":"EW Campion","year":"1987","unstructured":"Campion, E. W., Glynn, R. J. & DeLabry, L. O. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am. J. Med. 82, 421\u2013426 (1987).","journal-title":"Am. J. Med."},{"key":"BFjhg201657_CR40","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/S0140-6736(09)60883-7","volume":"375","author":"P Richette","year":"2010","unstructured":"Richette, P. & Bardin, T. Gout. Lancet 375, 318\u2013328 (2010).","journal-title":"Lancet"}],"container-title":["Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/jhg201657.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/jhg201657","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/jhg201657.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T17:35:49Z","timestamp":1684431349000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/jhg201657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,26]]},"references-count":40,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["BFjhg201657"],"URL":"https:\/\/doi.org\/10.1038\/jhg.2016.57","relation":{},"ISSN":["1434-5161","1435-232X"],"issn-type":[{"value":"1434-5161","type":"print"},{"value":"1435-232X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,26]]},"assertion":[{"value":"20 January 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2016","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}