{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:21:22Z","timestamp":1790367682920,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T00:00:00Z","timestamp":1563753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2016YFC1000501"],"award-info":[{"award-number":["2016YFC1000501"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472987"],"award-info":[{"award-number":["81472987"]}],"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":["81773441"],"award-info":[{"award-number":["81773441"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2019,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Neural tube defects (NTDs) are the most common severe birth defects with complex etiologies. Previous studies conducted on animals have suggested that the <jats:italic>Grhl3<\/jats:italic> gene is essential for closure of the spinal neural tube, but little evidence from human studies on the variants of <jats:italic>GRHL3<\/jats:italic> gene has been provided, especially the common genetic variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate the relationship between common genetic variants of <jats:italic>GRHL3<\/jats:italic> and the risk for NTDs, we performed a case\u2013control study and a case\u2013parent triad\/control study. Fast\u2010target enrichment sequencing was performed to screen exon regions from 503 NTD cases, and three tag SNPs (single nucleotide polymorphisms, including rs12030057, rs2486668, and rs545809) were selected according to the sequencing results. Then, Sequenom MassARRAY genotyping was performed in 757 case parents and 519 controls to obtain genotype information of the target variant sites among all NTD triads and controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The genotype distributions of all SNPs were in accordance with Hardy\u2013Weinberg Equilibrium (HWE) in the control population. In the case\u2013control study, significant associations were found between C27G genetic variants on rs2486668 and risk for spina bifida and encephalocele, respectively, under different genetic models. Consistently, in the case\u2013parent triad\/control study, GG genotype on rs2486668 was associated with increased risk for spina bifida, with a RR of 2.15 (95% CI: 1.20\u20133.83). However, no parent\u2010of\u2010origin effect was found for any tag SNPs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The <jats:italic>GRHL3<\/jats:italic> C67G missense variant may increase the risk for spina bifida and encephalocele phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1556","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T03:49:50Z","timestamp":1563853790000},"page":"1468-1478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic variants in <i>GRHL3<\/i> and risk for neural tube defects: A case\u2013control and case\u2013parent triad\/control study"],"prefix":"10.1002","volume":"111","author":[{"given":"Wenlei","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Reproductive and Child Health, NHC Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health Peking University Health Science Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhui","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, NHC Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health Peking University Health Science Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Tian","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, NHC Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health Peking University Health Science Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Jin","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, NHC Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health Peking University Health Science Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2033-9277","authenticated-orcid":false,"given":"Linlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, NHC Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health Peking University Health Science Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiguo","family":"Ren","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, NHC Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health Peking University Health Science Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10995-014-1542-8"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.ip71"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2009.06.001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23153"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1986"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20632"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.06.008"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2643"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20690"},{"issue":"24","key":"e_1_2_7_11_1","first-page":"4218","article-title":"Over\u2010expression of Grainyhead\u2010like 3 causes spina bifida and interacts genetically with mutant alleles of Grhl2 and Vangl2 in mice","volume":"27","author":"De Castro S. C. P.","year":"2018","journal-title":"Human Molecular Genetics"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2018.01.016"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/org.7.3.18431"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/429225"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a008982"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.235"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/ahg.12224"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-062012-170354"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp347"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20494"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm221"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20676"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2014-306175"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31380"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3543"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a071187"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23214"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20248"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23486"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17898-7"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90133-A"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38611"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.07.017"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320580406"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm961"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1086\/302708"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg644"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00123"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1086\/302337"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1086\/302466"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1086\/496900"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(02)00046-1"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-120213-092208"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100814-125315"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.000380"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151586"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.06322"}],"container-title":["Birth Defects Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.1556","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bdr2.1556","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.1556","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T12:57:32Z","timestamp":1694177852000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdr2.1556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,22]]},"references-count":46,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2019,11,15]]}},"alternative-id":["10.1002\/bdr2.1556"],"URL":"https:\/\/doi.org\/10.1002\/bdr2.1556","archive":["Portico"],"relation":{},"ISSN":["2472-1727","2472-1727"],"issn-type":[{"value":"2472-1727","type":"print"},{"value":"2472-1727","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,22]]},"assertion":[{"value":"2019-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}