ADAP1 – Crohn disease

Genetic studies in East Asian populations have robustly implicated ADAP1 in the susceptibility to Crohn disease. Two independent genome‑wide association studies (GWAS) identified ADAP1 as a shared risk locus in meta‑analyses involving 1,621 Crohn disease cases (PMID:35512355) and an additional 738 cases in replication cohorts (PMID:35512355) as well as in a large IBD study including over 14,000 cases (PMID:37156999). These analyses reported statistically significant associations, indicating that ADAP1 contributes to Crohn disease susceptibility in a polygenic context.

While traditional segregation data are not available given the complex nature of the disease, the genetic evidence is reinforced by the recurrence of the association signal across independent cohorts and populations. Although a precise HGVS‐coded variant was not provided in these studies, the genomic locus has been consistently implicated, which underscores the robustness of the association.

Functional studies further support the role of ADAP1 in biological processes that may intersect with disease mechanisms. In a zebrafish model, adap1‑deficient mutants generated by frameshift mutations around codon 120 exhibited altered social behaviors (PMID:40088134). These findings, while not directly recapitulating the gastrointestinal pathology of Crohn disease, suggest that ADAP1 plays a role in key signaling or regulatory pathways that warrant further investigation in the context of immune regulation and inflammation.

The convergence of multiple independent genetic studies with supportive functional data provides a strong case for the role of ADAP1 in Crohn disease. Although the functional model does not fully mimic intestinal pathology, the genetic association has been identified consistently and at genome‑wide significance. Thus, the existing evidence supports the utility of ADAP1 as a biomarker for Crohn disease risk, with potential implications for diagnostic decision‑making and future therapeutic research.

Key take‑home sentence: ADAP1 represents a genetically validated risk locus for Crohn disease, with converging evidence from large-scale GWAS and supportive functional models that reinforce its clinical utility.

References

• Human Molecular Genetics • 2022 • Identification of shared loci associated with both Crohn's disease and leprosy in East Asians PMID:35512355
• Nature Genetics • 2023 • Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries PMID:37156999
• Development, Growth & Differentiation • 2025 • Establishment and characterization of adap1‑deficient zebrafish PMID:40088134

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