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Fortuitously, the association between folic acid and NTDs became widely accepted in the early 1990s, at a time when genetic association studies of complex traits were becoming increasingly feasible. The confluence of these events has had a major impact on the direction of epidemiological, NTD research. Association studies to evaluate genes that may influence the risk of NTDs through their role in folate\u2010related processes, or through other metabolic or developmental pathways are now commonplace. Moreover, the study of genetic as well as non\u2010genetic, factors that may influence NTD risk through effects on the nutrient status of the mother or embryo has emerged as a major research focus. Research efforts over the past decade indicate that gene\u2013gene, gene\u2013environment, and higher\u2010order interactions, as well as maternal genetic effects influence NTD risk, highlighting the complexity of the factors that underlie these conditions. The challenge for the future is to design studies that address these complexities, and are adequately powered to detect the factors or combination of factors that influence the development of NTDs. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.c.30057","type":"journal-article","created":{"date-parts":[[2005,3,30]],"date-time":"2005-03-30T21:48:08Z","timestamp":1112219288000},"page":"88-94","source":"Crossref","is-referenced-by-count":235,"title":["Epidemiology of neural tube defects"],"prefix":"10.1002","volume":"135C","author":[{"given":"Laura E.","family":"Mitchell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,3,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)03248-1"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.55.11.845"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320170132"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/oem.59.2.92"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420420409"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199911113412006"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000056005"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/02724939992310"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a008647"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1019722011688"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023079326786"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwg286"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.10.3.209"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1071255"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20230"},{"key":"e_1_2_6_17_1","first-page":"1","article-title":"Surveillance for anencephaly and spina bifida and the impact of prenatal diagnosis\u2014United States, 1985\u20131994","volume":"44","author":"CDC","year":"1995","journal-title":"MMWR"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199812)58:6<251::AID-TERA6>3.0.CO;2-L"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.307.6906.703"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199212243272602"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10080"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200946"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10124"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/oem.58.7.443"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)01352-X"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/344209"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.28.9.605"},{"key":"e_1_2_6_28_1","first-page":"1","article-title":"Folic acid and prevention of spina bifida and anencephaly. 10 years after the U.S. Public Health Service Recommendation. 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