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Genome-wide association study (GWAS) models compared allele frequencies across fortification eras among all participants (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091285), the subset with CTHD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009534), and the remaining individuals with other heart defects (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009751). Functional enrichment was assessed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Among the full analytic group, eight loci had at least two suggestive variants before compared to after fortification. Among the subset with CTHD, two variants located in\n                    <jats:italic>DHRS3<\/jats:italic>\n                    (rs7551703, odds ratio [OR] 2.10, and rs6541043, OR 2.21) and four variants located in\n                    <jats:italic>PPARGC1B<\/jats:italic>\n                    showed suggestive association after fortification (OR 4.47\u20134.51). Enriched biological pathway terms were consistent with cardiac developmental processes. In summary, this study examined the association between folic acid fortification and genetic risk for CTHD and other heart defects and identified associations with fortification era that suggest some shift in risk following fortification. Identified pathways suggest gene-nutrient interactions may modulate cardiac developmental pathways, underscoring the relationship between maternal folate status and cardiovascular development.\n                  <\/jats:p>","DOI":"10.1007\/s00439-026-02888-5","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:07:35Z","timestamp":1792652855000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The impact of nationwide folic acid fortification on genetic variants associated with conotruncal heart defects"],"prefix":"10.1007","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7816-2646","authenticated-orcid":false,"given":"Sarah U.","family":"Morton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Mondragon-Estrada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omobola O.","family":"Oluwafemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kit Sing","family":"Au","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hope","family":"Northrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy K.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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