{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T13:39:36Z","timestamp":1783431576758,"version":"3.54.6"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T00:00:00Z","timestamp":1487030400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T00:00:00Z","timestamp":1487030400000},"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 recent genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in European cohorts has identified six susceptibility loci mapping to 11q22.1 (<jats:italic>YAP1<\/jats:italic>), 2p21 (<jats:italic>THADA<\/jats:italic>), 11p14.1 (<jats:italic>FSHB<\/jats:italic>), 2q34 (<jats:italic>ERBB4<\/jats:italic>), 12q21.2 (<jats:italic>KRR1<\/jats:italic>), and 5q31.1 (<jats:italic>RAD50<\/jats:italic>). The loci of 11q22.1, 2p21 and 11p14.1 have been confirmed to be associated with PCOS in Chinese; whereas the other three new loci (2q34, 12q21.2, and 5q31.1) still need to be evaluated in Chinese. This study was aimed to determine if the three new loci identified in European PCOS also confer risks for PCOS in Han Chinese. We performed a case-control genetic association study comprising 1500 PCOS cases and 1220 age-matched control subjects. Marker SNPs rs1351592 (2q34, <jats:italic>ERBB4<\/jats:italic>), rs1275468 (12q21.2, <jats:italic>KRR1<\/jats:italic>) and rs13164856 (5q31.1, <jats:italic>RAD50<\/jats:italic>) were genotyped using TaqMan-MGB probe assay. Genotyping analysis showed the allele frequency of rs1351592 in gene <jats:italic>ERBB4<\/jats:italic> was significantly different (<jats:italic>P<\/jats:italic>\u2009=\u20091.05E-03) between PCOS cases and control group, and remained significant even after BMI adjustment (<jats:italic>P<\/jats:italic><jats:sub>adjusted<\/jats:sub>\u2009=\u20092.09E-04). However, the allele frequencies of the other two risk variants, rs1275468 (12q21.2, <jats:italic>KRR1<\/jats:italic>) and rs13164856 (5q31.1, <jats:italic>RAD50<\/jats:italic>), were not significantly different in the replication cohort. Our results demonstrate that <jats:italic>ERBB4<\/jats:italic>, with the strongest association in European PCOS, also confers risk for PCOS in Han Chinese.<\/jats:p>","DOI":"10.1038\/srep42000","type":"journal-article","created":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T10:18:34Z","timestamp":1487067514000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["ERBB4 Confers Risk for Polycystic Ovary Syndrome in Han Chinese"],"prefix":"10.1038","volume":"7","author":[{"given":"Yingqian","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizhen","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Jiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,14]]},"reference":[{"key":"BFsrep42000_CR1","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/nrendo.2010.217","volume":"7","author":"MO Goodarzi","year":"2011","unstructured":"Goodarzi, M. O., Dumesic, D. A., Chazenbalk, G. & Azziz, R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 7, 219\u201331 (2011).","journal-title":"Nat Rev Endocrinol"},{"key":"BFsrep42000_CR2","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1093\/humrep\/deh098","volume":"19","author":"Revised","year":"2004","unstructured":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Human Reproduction 19, 41\u201347 (2004).","journal-title":"Human Reproduction"},{"key":"BFsrep42000_CR3","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/ng.732","volume":"43","author":"Z Chen","year":"2010","unstructured":"Chen, Z. et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nature Genetics 43, 55\u201359 (2010).","journal-title":"Nature Genetics"},{"key":"BFsrep42000_CR4","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1038\/ng.2384","volume":"44","author":"Y Shi","year":"2012","unstructured":"Shi, Y. et al. Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Nature Genetics 44, 1020\u20131025 (2012).","journal-title":"Nature Genetics"},{"key":"BFsrep42000_CR5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.fertnstert.2016.04.040","volume":"106","author":"MR Jones","year":"2016","unstructured":"Jones, M. R. & Goodarzi, M. O. Genetic determinants of polycystic ovary syndrome: progress and future directions. Fertility and Sterility 106, 25\u201332 (2016).","journal-title":"Fertility and Sterility"},{"key":"BFsrep42000_CR6","doi-asserted-by":"publisher","first-page":"E182","DOI":"10.1210\/jc.2014-2689","volume":"100","author":"MA Brower","year":"2015","unstructured":"Brower, M. A. et al. Further Investigation in Europeans of Susceptibility Variants for Polycystic Ovary Syndrome Discovered in Genome-Wide Association Studies of Chinese Individuals. The Journal of Clinical Endocrinology & Metabolism 100, E182\u2013E186 (2015).","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"BFsrep42000_CR7","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1002\/iub.1457","volume":"68","author":"AS El-Shal","year":"2016","unstructured":"El-Shal, A. S., Zidan, H. E., Rashad, N. M., Abdelaziz, A. M. & Harira, M. M. Association between genes encoding components of the Leutinizing hormone\/Luteinizing hormone-choriogonadotrophin receptor pathway and polycystic ovary syndrome in Egyptian women. IUBMB Life 68, 23\u201336 (2016).","journal-title":"IUBMB Life"},{"key":"BFsrep42000_CR8","doi-asserted-by":"publisher","first-page":"7502","DOI":"10.1038\/ncomms8502","volume":"6","author":"MG Hayes","year":"2015","unstructured":"Hayes, M. G. et al. Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Nature Communications 6, 7502 (2015).","journal-title":"Nature Communications"},{"key":"BFsrep42000_CR9","doi-asserted-by":"publisher","first-page":"2178","DOI":"10.1210\/jc.2015-3776","volume":"101","author":"Y Tian","year":"2016","unstructured":"Tian, Y. et al. Variants in FSHB Are Associated With Polycystic Ovary Syndrome and Luteinizing Hormone Level in Han Chinese Women. The Journal of Clinical Endocrinology & Metabolism 101, 2178\u20132184 (2016).","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"BFsrep42000_CR10","doi-asserted-by":"publisher","first-page":"8464","DOI":"10.1038\/ncomms9464","volume":"6","author":"FR Day","year":"2015","unstructured":"Day, F. R. et al. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nature Communications 6, 8464 (2015).","journal-title":"Nature Communications"},{"key":"BFsrep42000_CR11","doi-asserted-by":"publisher","first-page":"E2006","DOI":"10.1210\/jc.2013-2495","volume":"98","author":"YV Louwers","year":"2013","unstructured":"Louwers, Y. V., Stolk, L., Uitterlinden, A. G. & Laven, J. S. E. Cross-Ethnic Meta-Analysis of Genetic Variants for Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology & Metabolism 98, E2006\u2013E2012 (2013).","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"BFsrep42000_CR12","doi-asserted-by":"publisher","first-page":"E185","DOI":"10.1210\/jc.2012-2471","volume":"98","author":"P Mutharasan","year":"2013","unstructured":"Mutharasan, P. et al. Evidence for Chromosome 2p16.3 Polycystic Ovary Syndrome Susceptibility Locus in Affected Women of European Ancestry. The Journal of Clinical Endocrinology & Metabolism 98, E185\u201390 (2013).","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"BFsrep42000_CR13","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1093\/humrep\/dev085","volume":"30","author":"R Saxena","year":"2015","unstructured":"Saxena, R. et al. Han Chinese polycystic ovary syndrome risk variants in women of European ancestry: relationship to FSH levels and glucose tolerance. Human Reproduction 30, 1454\u20131459 (2015).","journal-title":"Human Reproduction"},{"key":"BFsrep42000_CR14","doi-asserted-by":"publisher","first-page":"E1342","DOI":"10.1210\/jc.2011-3478","volume":"97","author":"CK Welt","year":"2012","unstructured":"Welt, C. K. et al. Variants in DENND1A Are Associated with Polycystic Ovary Syndrome in Women of European Ancestry. The Journal of Clinical Endocrinology & Metabolism 97, E1342\u2013E1347 (2012).","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"BFsrep42000_CR15","doi-asserted-by":"publisher","first-page":"a020768","DOI":"10.1101\/cshperspect.a020768","volume":"6","author":"MA Lemmon","year":"2014","unstructured":"Lemmon, M. A., Schlessinger, J. & Ferguson, K. M. The EGFR Family: Not So Prototypical Receptor Tyrosine Kinases. Cold Spring Harbor Perspectives in Biology 6, a020768\u2013a020768 (2014).","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"BFsrep42000_CR16","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.semcdb.2014.03.005","volume":"28","author":"DJ Riese","year":"2014","unstructured":"Riese, D. J. & Cullum, R. L. Epiregulin: Roles in normal physiology and cancer. Seminars in Cell & Developmental Biology 28, 49\u201356 (2014).","journal-title":"Seminars in Cell & Developmental Biology"},{"key":"BFsrep42000_CR17","doi-asserted-by":"crossref","unstructured":"Jamnongjit, M., Gill, A. & Hammes, S. R. Epidermal growth factor receptor signaling is required for normal ovarian steroidogenesis and oocyte maturation. Proceedings of the National Academy of Sciences (2005).","DOI":"10.1073\/pnas.0508521102"},{"key":"BFsrep42000_CR18","doi-asserted-by":"publisher","first-page":"2708","DOI":"10.1093\/humrep\/dei162","volume":"20","author":"Y Akayama","year":"2005","unstructured":"Akayama, Y. Gene expression and immunolocalization of heparin-binding epidermal growth factor-like growth factor and human epidermal growth factor receptors in human corpus luteum. Human Reproduction 20, 2708\u20132714 (2005).","journal-title":"Human Reproduction"},{"key":"BFsrep42000_CR19","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1055\/s-2007-992919","volume":"26","author":"MO Goodarzi","year":"2008","unstructured":"Goodarzi, M. O. Looking for polycystic ovary syndrome genes: rational and best strategy. Semin Reprod Med 26, 5\u201313 (2008).","journal-title":"Semin Reprod Med"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep42000.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep42000","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep42000.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T01:39:28Z","timestamp":1671845968000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep42000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,14]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,2,24]]}},"alternative-id":["BFsrep42000"],"URL":"https:\/\/doi.org\/10.1038\/srep42000","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,14]]},"assertion":[{"value":"22 November 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2017","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":"42000"}}