{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:58:38Z","timestamp":1790974718255,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,12,10]],"date-time":"2010-12-10T00:00:00Z","timestamp":1291939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Individual studies of the genetics of neural tube defects (NTDs) contain results on a small number of genes in each report. To identify genetic risk factors for NTDs, we evaluated potentially functional single nucleotide polymorphisms (SNPs) that are biologically plausible risk factors for NTDs but that have never been investigated for an association with NTDs, examined SNPs that previously showed no association with NTDs in published studies, and tried to confirm previously reported associations in folate\u2010related and non\u2010folate\u2010related genes. We investigated 64 SNPs in 34 genes for association with spina bifida in up to 558 case families (520 cases, 507 mothers, 457 fathers) and 994 controls in Ireland. Case\u2010control and mother\u2010control comparisons of genotype frequencies, tests of transmission disequilibrium, and log\u2010linear regression models were used to calculate effect estimates. Spina bifida was associated with over\u2010transmission of the <jats:italic>LEPR<\/jats:italic> (leptin receptor) rs1805134 minor C allele [genotype relative risk (GRR): 1.5; 95% confidence interval (CI): 1.0\u20132.1; <jats:italic>P<\/jats:italic>\u2009=\u20090.0264] and the <jats:italic>COMT<\/jats:italic> (catechol\u2010<jats:italic>O<\/jats:italic>\u2010methyltransferase) rs737865 major T allele (GRR: 1.4; 95% CI: 1.1\u20132.0; <jats:italic>P<\/jats:italic>\u2009=\u20090.0206). After correcting for multiple comparisons, these individual test <jats:italic>P<\/jats:italic>\u2010values exceeded 0.05. Consistent with previous reports, spina bifida was associated with <jats:italic>MTHFR<\/jats:italic> 677C&gt;T, T (Brachyury) rs3127334, <jats:italic>LEPR<\/jats:italic> K109R, and <jats:italic>PDGFRA<\/jats:italic> promoter haplotype combinations. The associations between <jats:italic>LEPR<\/jats:italic> SNPs and spina bifida suggest a possible mechanism for the finding that obesity is a NTD risk factor. The association between a variant in <jats:italic>COMT<\/jats:italic> and spina bifida implicates methylation and epigenetics in NTDs. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33755","type":"journal-article","created":{"date-parts":[[2010,12,10]],"date-time":"2010-12-10T20:03:47Z","timestamp":1292011427000},"page":"14-21","source":"Crossref","is-referenced-by-count":37,"title":["Evaluation of 64 candidate single nucleotide polymorphisms as risk factors for neural tube defects in a large Irish study population"],"prefix":"10.1002","volume":"155","author":[{"given":"Tonia C.","family":"Carter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith","family":"Pangilinan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Troendle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Molloy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"VanderMeer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peadar N.","family":"Kirke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary R.","family":"Conley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Shane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence C.","family":"Brody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Mills","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,12,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.1999.2881"},{"key":"e_1_2_6_5_1","first-page":"4048","article-title":"Transport of methotrexate, methotrexate polyglutamates, and 17beta\u2010estradiol 17\u2010(beta\u2010D\u2010glucuronide) by ABCG2: Effects of acquired mutations at R482 on methotrexate transport","volume":"63","author":"Chen ZS","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/383407a0"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199212243272602"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719107309590"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20183"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/109065799316572"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/22.10.1661"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0296-191"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.113.3.913"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20143"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31212"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/84867"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2007.00377.x"},{"key":"e_1_2_6_18_1","first-page":"703","article-title":"Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects","volume":"86","author":"Kirke PN","year":"1993","journal-title":"Q J Med"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38036.646030.EE"},{"key":"e_1_2_6_20_1","first-page":"5493","article-title":"An association between the allele coding for a low activity variant of catechol\u2010O\u2010methyltransferase and the risk for breast cancer","volume":"57","author":"Lavigne JA","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jech.53.12.782"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)90165-5"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20520"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.5.669"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90133-A"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81656-6"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30713"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.073775"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-003-0008-4"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.3.e14"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21090"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.GIM.0000151158.09278.2B"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(200003)61:3<231::AID-TERA11>3.0.CO;2-L"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-10-49"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1086\/302310"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000529)92:3<206::AID-AJMG9>3.0.CO;2-W"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.14.2691"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10436"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20574"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30700"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(94)70224-1"},{"key":"e_1_2_6_42_1","first-page":"988","article-title":"Neural tube defects among twin births","volume":"34","author":"Windham GC","year":"1982","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2003.11.003"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.33755","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.33755","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T18:19:32Z","timestamp":1697653172000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.33755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12,10]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,1]]}},"alternative-id":["10.1002\/ajmg.a.33755"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.33755","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,12,10]]}}}