From Diet to DNA: A Data-Driven Nutrigenomic Analysis of CTLA4 and MYO9B
Lauren Athon (Graceland University)
Mutations and polymorphisms in CTLA4 and MYO9B have both been associated with celiac disease and other autoimmune conditions, yet their genetic mechanisms and potential overlap remain difficult to see when transcript models, clinical variants, and association data are considered separately. Celiac disease is a diet-triggered disorder, which makes it a useful nutrigenomic case study: gluten exposure interacts with genetic and regulatory variation to shape mucosal immune responses. This work presents an exploratory pipeline that integrates NCBI RefSeq (curated isoforms and metadata), Ensembl (broader transcript annotations via biomaRt), ClinVar (clinical assertions), and the GWAS Catalog (celiac-associated loci, ontology EFO_0001060) to compare CTLA4 and MYO9B side by side. Sequence concordance checks link Ensembl cDNA to RefSeq mRNA (and peptide-to-protein summaries where applicable); ClinVar variants are mapped onto transcripts with interval overlaps; GWAS hits are summarized relative to gene coordinates. Mixed variant metadata are explored with factor analysis of mixed data (FAMD) after Gower-distance clustering (partitioning around medoids, PAM), using variant type, submission origin, gene-relative position, and related engineered features. In this dataset, MYO9B exhibits greater annotated transcript diversity and a larger ClinVar burden, while celiac GWAS signals localize to intergenic regions near CTLA4—consistent with cis-regulatory mechanisms rather than coding disruption alone. The FAMD ordination (Figure 3) separates variants into clusters that summarize joint patterns of clinical significance, variant class, origin, and location within each gene—supporting interpretation of ClinVar structure beyond single-variable tabulations. The contribution is a reproducible workflow and a set of exploratory findings that can seed nutrigenomic follow-up (for example tissue eQTLs, enhancer annotation, and diet-linked pathway interpretation).