ArticleResearch square2026
The impact of nationwide folic acid fortification on genetic variants associated with conotruncal heart defects.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors.
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Abstract
Folate deficiency is associated with an increased risk of conotruncal heart defects (CTHD), but interactions with genetic factors remain unclear. Our objective was to investigate genome-wide associations between genetic variants and birth before versus after universal folic acid fortification among children with CTHD and other heart defects. Genetic sequencing data were available through the Pediatric Cardiac Genomics Consortium. Sequencing data were aligned to the human reference genome (GRCh38/hg38) and jointly processed to ensure uniform variant detection and minimize batch effects. Analyses were restricted to individuals with European-inferred genetic ancestry. GWAS models were implemented to explore the association of common variants with fortification eras among all participants (n=1285), the subset of individuals with CTHD (n=534), and the remaining individuals with other heart defects (n=751). 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 nominally-enriched variants before compared to after fortification. Among the subset with CTHD, two variants located in
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