{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T13:12:38Z","timestamp":1772802758313,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T00:00:00Z","timestamp":1517184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81601423"],"award-info":[{"award-number":["81601423"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81600399"],"award-info":[{"award-number":["81600399"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004000","name":"Guangzhou Science and Technology Program key projects","doi-asserted-by":"publisher","award":["No.201707010014"],"award-info":[{"award-number":["No.201707010014"]}],"id":[{"id":"10.13039\/501100004000","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hirschsprung disease (HSCR) is a genetic disorder characterized by the absence of enteric ganglia. There are more than 15 genes identified as contributed to HSCR by family\u2010based or population\u2010based approaches. However, these findings were not fulfilled to explain the heritability of most sporadic cases. In this study, using 1470 HSCR and 1473 control subjects in South Chinese population, we replicated two variants in <jats:italic>NRG1<\/jats:italic> (rs16879552, <jats:italic>P<\/jats:italic>\u00a0=\u00a01.05E\u201004 and rs7835688, <jats:italic>P<\/jats:italic>\u00a0=\u00a01.19E\u201007), and further clarified the two replicated SNPs were more essential for patients with short\u2010segment aganglionosis (SHSCR) (<jats:italic>P<\/jats:italic>\u00a0=\u00a02.37E\u201005). We also tried to replicate the most prominent signal (rs7785360) in <jats:italic>AUTS2<\/jats:italic>, which was a potential susceptibility gene with HSCR. In our results, in terms of individual association, marginal effect was observed to affect the HSCR patients following recessive model (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.089). Noteworthy, significant intergenic synergistic effect between rs16879552 (<jats:italic>NRG1<\/jats:italic>) and rs7785360 (<jats:italic>AUTS2<\/jats:italic>) was identified through cross\u2010validation by logistic regression (<jats:italic>P<\/jats:italic>\u00a0=\u00a02.45E\u201003, OR\u00a0=\u00a01.53) and multifactor dimensionality reduction (MDR, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001, OR\u00a0=\u00a01.77). Significant correlation was observed between expression of these two genes in the normal segments of the colons (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.018), together with differential expression of these genes between aganglionic colonic segments and normal colonic segments of the HSCR patients (<jats:italic>P<\/jats:italic> value for <jats:italic>AUTS2<\/jats:italic> &lt;0.0001, <jats:italic>P<\/jats:italic> value for <jats:italic>NRG1\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.0243). Although functional evaluation is required, we supply new evidence for the <jats:italic>NRG1<\/jats:italic> to HSCR and raised up a new susceptibility gene <jats:italic>AUTS2<\/jats:italic> to a specific symptom for the disease.<\/jats:p>","DOI":"10.1111\/jcmm.13498","type":"journal-article","created":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T22:12:59Z","timestamp":1517263979000},"page":"2190-2199","source":"Crossref","is-referenced-by-count":9,"title":["Association of <i>NRG1<\/i> and <i>AUTS2<\/i> genetic polymorphisms with Hirschsprung disease in a South Chinese population"],"prefix":"10.1111","volume":"22","author":[{"given":"Yan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoli","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jixiao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruizhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deli","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0103-1672","authenticated-orcid":false,"given":"Huimin","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1994.tb12955.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2013.03.001"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.053959"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2013.05.019"},{"key":"e_1_2_7_6_1","first-page":"5265","article-title":"Trans\u2010ethnic meta\u2010analysis of genome\u2010wide association studies for Hirschsprung disease","volume":"25","author":"Tang CS","year":"2016","journal-title":"Hum Mol 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