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Nonetheless, some individuals fail to respond to FA supplementation; hence NTDs remain a significant public health concern. The mechanisms that underlie the beneficial effects of FA supplementation remain poorly understood. Mouse models have been used extensively to study the mechanisms driving neural tube closure (NTC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Microarray data of GSE51285 was downloaded from the NCBI GEO database, which contains the RNA expression profiles of livers from five NTD mouse mutants (heterozygous females) and their corresponding wildtype (WT) controls. Those five NTD mutants have different responsiveness to FA supplementation. The differentially expressed genes (DEGs) between NTD heterozygous and WT mice, as well as the DEGs between FA\u2010responsive and FA\u2010resistant mutants were carefully examined. Weighted gene correlation network analysis (WGCNA) was performed in order to identify genes with high correlations to either FA responsiveness or NTDs, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, we identified 18 genes related to the pathogenesis of NTDs, as well as 55 genes related to FA responsiveness. Eight more candidate genes (<jats:italic>Abcc3, Gsr, Gclc, Mthfd1, Gart, Bche, Slc25a32<\/jats:italic>, and <jats:italic>Slc44a2<\/jats:italic>) were identified by examining the DEGs of those genes involved in the extended folate metabolic pathway between FA\u2010responsive and FA\u2010resistant mutants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Those genes are involved in mitochondrial choline metabolism, de novo purine synthesis, and glutathione generation, suggesting that formate, choline, and manipulating antioxidant levels may be effective interventions in FA\u2010resistant NTDs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1336","type":"journal-article","created":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T06:36:52Z","timestamp":1525675012000},"page":"982-993","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Network correlation analysis revealed potential new mechanisms for neural tube defects beyond folic acid"],"prefix":"10.1002","volume":"110","author":[{"given":"Xiaoya","family":"Gao","sequence":"first","affiliation":[{"name":"Institute of Developmental Biology &amp; Molecular Medicine, School of Life Sciences Fudan University Shanghai China"},{"name":"State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, School of Life Sciences Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard H.","family":"Finnell","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Biology and Medicine Baylor College of Medicine Houston Texas"},{"name":"Collaborative Innovation Center for Genetics &amp; Development, School of Life Sciences Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, School of Life Sciences Fudan University Shanghai China"},{"name":"Obstetrics and Gynecology Hospital Institute of Reproduction and Development, Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0488-2624","authenticated-orcid":false,"given":"Yufang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Developmental Biology &amp; 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