{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T12:23:04Z","timestamp":1775305384462,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T00:00:00Z","timestamp":1465862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T00:00:00Z","timestamp":1465862400000},"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><jats:p>A single-nucleotide polymorphism (SNP) rs4236601 at the <jats:italic>CAV1\/CAV2<\/jats:italic> locus is associated with primary open-angle glaucoma (POAG). Rs4236601 is common in Caucasians but rare in East Asians. Here we conducted a haplotype-tagging SNP analysis followed by replication in a total of 848 POAG cases and 1574 controls drawn from 3 cities in China and 1 city in Japan. Two SNPs, rs4236601 (odds ratio [OR]\u2009=\u20096.25; P\u2009=\u20090.0086) and a tagging-SNP rs3801994 (OR\u2009=\u20091.32; P\u2009=\u20090.042), were associated with POAG in the Hong Kong Chinese cohort after age and gender adjustments. Rs4236601 was associated with POAG also in Shantou (OR\u2009=\u20096.09; P\u2009=\u20090.0037) and Beijing (OR\u2009=\u20093.92; P\u2009=\u20090.030) cohorts after age and gender adjustment, with a pooled-OR of 5.26 (P\u2009=\u20099.0\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>) in Chinese; but it is non-polymorphic in the Osaka cohort. SNP rs3801994 showed a similar trend of effect in the Shantou and Beijing cohorts, with a pooled-OR of 1.23 (P\u2009=\u20090.022) and 1.20 (P\u2009=\u20090.063) in Chinese, prior to and after age and gender adjustment, respectively; but it showed a reverse effect in the Osaka cohort (OR\u2009=\u20090.58; P\u2009=\u20090.033) after the adjustments. We have thus confirmed the association of rs4236601 with POAG in different Chinese cohorts. Also, we found a common SNP rs3801994 of diverse associations with POAG between Chinese and Japanese.<\/jats:p>","DOI":"10.1038\/srep27837","type":"journal-article","created":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T11:38:55Z","timestamp":1465904335000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Ethnic specific association of the CAV1\/CAV2 locus with primary open-angle glaucoma"],"prefix":"10.1038","volume":"6","author":[{"given":"Shi Song","family":"Rong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li Jia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher K. S.","family":"Leung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Matsushita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyun","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuya","family":"Miki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia W. Y.","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pancy O. S.","family":"Tam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriyasu","family":"Hashida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvin L.","family":"Young","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motokazu","family":"Tsujikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingzhi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningli","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohji","family":"Nishida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi Pui","family":"Pang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,6,14]]},"reference":[{"key":"BFsrep27837_CR1","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1056\/NEJMra0804630","volume":"360","author":"YH Kwon","year":"2009","unstructured":"Kwon, Y. H., Fingert, J. H., Kuehn, M. H. & Alward, W. L. Primary open-angle glaucoma. N Engl J Med 360, 1113\u20131124 (2009).","journal-title":"N Engl J Med"},{"key":"BFsrep27837_CR2","first-page":"844","volume":"82","author":"S Resnikoff","year":"2004","unstructured":"Resnikoff, S. et al. Global data on visual impairment in the year 2002. Bull World Health Organ 82, 844\u2013851 (2004).","journal-title":"Bull World Health Organ"},{"key":"BFsrep27837_CR3","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.clinbiochem.2005.11.001","volume":"39","author":"BJ Fan","year":"2006","unstructured":"Fan, B. J., Wang, D. Y., Lam, D. S. & Pang, C. P. Gene mapping for primary open angle glaucoma. Clin Biochem 39, 249\u2013258 (2006).","journal-title":"Clin Biochem"},{"key":"BFsrep27837_CR4","doi-asserted-by":"publisher","first-page":"3064","DOI":"10.1172\/JCI43085","volume":"120","author":"BJ Fan","year":"2010","unstructured":"Fan, B. J. & Wiggs, J. L. Glaucoma: genes, phenotypes and new directions for therapy. J Clin Invest 120, 3064\u20133072 (2010).","journal-title":"J Clin Invest"},{"key":"BFsrep27837_CR5","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.preteyeres.2013.09.001","volume":"37","author":"SF Janssen","year":"2013","unstructured":"Janssen, S. F. et al. The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms and pathobiology. Prog Retin Eye Res 37, 31\u201367 (2013).","journal-title":"Prog Retin Eye Res"},{"key":"BFsrep27837_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10384-013-0286-0","volume":"58","author":"M Takamoto","year":"2014","unstructured":"Takamoto, M. & Araie, M. Genetics of primary open angle glaucoma. Jpn J Ophthalmol 58, 1\u201315 (2014).","journal-title":"Jpn J Ophthalmol"},{"key":"BFsrep27837_CR7","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/ng.661","volume":"42","author":"G Thorleifsson","year":"2010","unstructured":"Thorleifsson, G. et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat Genet 42, 906\u2013909 (2010).","journal-title":"Nat Genet"},{"key":"BFsrep27837_CR8","first-page":"430","volume":"17","author":"MH Kuehn","year":"2011","unstructured":"Kuehn, M. H. et al. Chromosome 7q31 POAG locus: ocular expression of caveolins and lack of association with POAG in a US cohort. Mol Vis 17, 430\u2013435 (2011).","journal-title":"Mol Vis"},{"key":"BFsrep27837_CR9","doi-asserted-by":"publisher","first-page":"4707","DOI":"10.1093\/hmg\/ddr382","volume":"20","author":"JL Wiggs","year":"2011","unstructured":"Wiggs, J. L. et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma in Caucasians from the USA. Hum Mol Genet 20, 4707\u20134713 (2011).","journal-title":"Hum Mol Genet"},{"key":"BFsrep27837_CR10","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.ophtha.2013.09.012","volume":"121","author":"SJ Loomis","year":"2014","unstructured":"Loomis, S. J. et al. Association of CAV1\/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss. Ophthalmology 121, 508\u2013516 (2014).","journal-title":"Ophthalmology"},{"key":"BFsrep27837_CR11","first-page":"548","volume":"21","author":"S Kim","year":"2015","unstructured":"Kim, S. et al. Expression-associated polymorphisms of CAV1-CAV2 affect intraocular pressure and high-tension glaucoma risk. Mol Vis 21, 548\u2013554 (2015).","journal-title":"Mol Vis"},{"key":"BFsrep27837_CR12","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/eye.2013.123","volume":"27","author":"T Kato","year":"2013","unstructured":"Kato, T. et al. Association study of genetic variants on chromosome 7q31 with susceptibility to normal tension glaucoma in a Japanese population. Eye (Lond) 27, 979\u2013983 (2013).","journal-title":"Eye (Lond)"},{"key":"BFsrep27837_CR13","doi-asserted-by":"publisher","first-page":"6248","DOI":"10.1167\/iovs.13-12779","volume":"54","author":"Y Liu","year":"2013","unstructured":"Liu, Y. et al. Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry. Invest Ophthalmol Vis Sci 54, 6248\u20136254 (2013).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"BFsrep27837_CR14","doi-asserted-by":"publisher","first-page":"8378","DOI":"10.1038\/srep08378","volume":"5","author":"SE Williams","year":"2015","unstructured":"Williams, S. E., Carmichael, T. R., Allingham, R. R., Hauser, M. & Ramsay, M. The genetics of POAG in black South Africans: a candidate gene association study. Sci Rep 5, 8378 (2015).","journal-title":"Sci Rep"},{"key":"BFsrep27837_CR15","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1038\/ng.2394","volume":"44","author":"E Grundberg","year":"2012","unstructured":"Grundberg, E. et al. Mapping cis- and trans-regulatory effects across multiple tissues in twins. Nat Genet 44, 1084\u20131089 (2012).","journal-title":"Nat Genet"},{"key":"BFsrep27837_CR16","doi-asserted-by":"publisher","first-page":"3978","DOI":"10.4161\/cc.8.23.10206","volume":"8","author":"JF Jasmin","year":"2009","unstructured":"Jasmin, J. F., Yang, M., Iacovitti, L. & Lisanti, M. P. Genetic ablation of caveolin-1 increases neural stem cell proliferation in the subventricular zone (SVZ) of the adult mouse brain. Cell Cycle 8, 3978\u20133983 (2009).","journal-title":"Cell Cycle"},{"key":"BFsrep27837_CR17","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1038\/3305","volume":"4","author":"PS Eriksson","year":"1998","unstructured":"Eriksson, P. S. et al. Neurogenesis in the adult human hippocampus. Nat Med 4, 1313\u20131317 (1998).","journal-title":"Nat Med"},{"key":"BFsrep27837_CR18","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/nature02301","volume":"427","author":"N Sanai","year":"2004","unstructured":"Sanai, N. et al. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427, 740\u2013744 (2004).","journal-title":"Nature"},{"key":"BFsrep27837_CR19","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1161\/01.RES.0000260180.42709.29","volume":"100","author":"JF Jasmin","year":"2007","unstructured":"Jasmin, J. F. et al. Caveolin-1 deficiency increases cerebral ischemic injury. Circ Res 100, 721\u2013729 (2007).","journal-title":"Circ Res"},{"key":"BFsrep27837_CR20","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.ajo.2010.01.018","volume":"149","author":"J Caprioli","year":"2010","unstructured":"Caprioli, J. & Coleman, A. L. Blood pressure, perfusion pressure and glaucoma. Am J Ophthalmol 149, 704\u2013712 (2010).","journal-title":"Am J Ophthalmol"},{"key":"BFsrep27837_CR21","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/S1350-9462(98)00037-8","volume":"18","author":"A Harris","year":"1999","unstructured":"Harris, A., Chung, H. S., Ciulla, T. A. & Kagemann, L. Progress in measurement of ocular blood flow and relevance to our understanding of glaucoma and age-related macular degeneration. Prog Retin Eye Res 18, 669\u2013687 (1999).","journal-title":"Prog Retin Eye Res"},{"key":"BFsrep27837_CR22","first-page":"1629","volume":"18","author":"LJ Chen","year":"2012","unstructured":"Chen, L. J. et al. SNP rs1533428 at 2p16.3 as a marker for late-onset primary open-angle glaucoma. Mol Vis 18, 1629\u20131639 (2012).","journal-title":"Mol Vis"},{"key":"BFsrep27837_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. Am J Hum Genet 81, 559\u2013575 (2007).","journal-title":"Am J Hum Genet"},{"key":"BFsrep27837_CR24","unstructured":"Breslow, N. E. & Day, N. E. Statistical Methods in Cancer Research. Vol. 1 - The Analysis of Case-Control Studies (IARC Scientific Publications, 1980)."},{"key":"BFsrep27837_CR25","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1056\/NEJMoa075819","volume":"358","author":"SL Zheng","year":"2008","unstructured":"Zheng, S. L. et al. Cumulative association of five genetic variants with prostate cancer. N Engl J Med 358, 910\u2013919 ((2008).","journal-title":"N Engl J Med"},{"key":"BFsrep27837_CR26","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1086\/383251","volume":"74","author":"DR Nyholt","year":"2004","unstructured":"Nyholt, D. R. A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 74, 765\u2013769 (2004).","journal-title":"Am J Hum Genet"},{"key":"BFsrep27837_CR27","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1002\/sim.1186","volume":"21","author":"JP Higgins","year":"2002","unstructured":"Higgins, J. P. & Thompson, S. G. Quantifying heterogeneity in a meta-analysis. Stat Med 21, 1539\u20131558 (2002).","journal-title":"Stat Med"},{"key":"BFsrep27837_CR28","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","volume":"327","author":"JP Higgins","year":"2003","unstructured":"Higgins, J. P., Thompson, S. G., Deeks, J. J. & Altman, D. G. Measuring inconsistency in meta-analyses. BMJ 327, 557\u2013560 (2003).","journal-title":"BMJ"},{"key":"BFsrep27837_CR29","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1146\/annurev.pu.09.050188.001011","volume":"9","author":"SJ Kuritz","year":"1988","unstructured":"Kuritz, S. J., Landis, J. R. & Koch, G. G. A general overview of Mantel-Haenszel methods: applications and recent developments. Annu Rev Public Health 9, 123\u2013160 (1988).","journal-title":"Annu Rev Public Health"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep27837","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep27837.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep27837.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T16:44:45Z","timestamp":1672850685000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep27837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,14]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,9,13]]}},"alternative-id":["BFsrep27837"],"URL":"https:\/\/doi.org\/10.1038\/srep27837","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,14]]},"assertion":[{"value":"15 January 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"27837"}}