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There is little known at present about any possible hypospadias risk associations in Han Chinese populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To systematically investigate hypospadias risk\u2013associated gene variants in Chinese patients, we performed the first GWAS in a Han Chinese cohort consisting of 197 moderate-severe hypospadias cases and 933 unaffected controls. Suggestive loci (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20091\u2009\u00d7\u200910\n                      <jats:sup>\u2212\u20094<\/jats:sup>\n                      ) were replicated in 118 cases and 383 controls, as well as in a second independent validation population of 137 cases and 190 controls. Regulatory and protein-protein interactions (PPIs) were then conducted for the functional analyses of candidate variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified rs11170516 with the risk allele G within the\n                      <jats:italic>SP1<\/jats:italic>\n                      \/\n                      <jats:italic>SP7<\/jats:italic>\n                      region that was independently associated with moderate-severe hypospadias [\n                      <jats:italic>SP1<\/jats:italic>\n                      \/\n                      <jats:italic>SP7<\/jats:italic>\n                      , rs11170516,\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>combine<\/jats:sub>\n                      \u2009=\u20093.5\u2009\u00d7\u200910\n                      <jats:sup>\u2212\u20099<\/jats:sup>\n                      , odds ratio (OR)\u2009=\u20091.96 (1.59\u20132.44)]. Results also suggested that rs11170516 is associated with the expression of\n                      <jats:italic>SP1<\/jats:italic>\n                      as a cis-expression quantitative trait locus (cis-eQTL). Protein SP1 could affect the risk of hypospadias via PPIs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We performed the first GWAS of moderate-severe hypospadias in a Han Chinese cohort, and identified one novel susceptibility\n                      <jats:italic>cis<\/jats:italic>\n                      -acting regulatory locus at 12q13.13, which may regulate a variety of hypospadias-related pathways by affecting proximal\n                      <jats:italic>SP1<\/jats:italic>\n                      gene expression and subsequent PPIs. This study complements known common hypospadias risk-associated variants and provides the possible role of\n                      <jats:italic>cis<\/jats:italic>\n                      -acting regulatory variant in causing hypospadias.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12920-019-0642-0","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T13:03:25Z","timestamp":1576760605000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Genome-wide association study in Chinese cohort identifies one novel hypospadias risk associated locus at 12q13.13"],"prefix":"10.1186","volume":"12","author":[{"given":"Zhongzhong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunping","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H.","family":"Finnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daru","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2298-2610","authenticated-orcid":false,"given":"Fang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,19]]},"reference":[{"issue":"3","key":"642_CR1","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/s004410000345","volume":"305","author":"LS Baskin","year":"2001","unstructured":"Baskin LS, Erol A, Jegatheesan P, Li Y, Liu W, Cunha GR. 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