LY75 and Crohn disease

This summary details the association between LY75 (HGNC:6729) and Crohn disease (MONDO_0005011). Two independent multi‐patient studies have significantly implicated LY75 in Crohn disease susceptibility. The first study, conducted in a Japanese cohort, genotyped 51 Crohn disease patients alongside ulcerative colitis patients and healthy controls, identifying a significant association with the rs16822581 SNP (PMID:27965521). The second study applied a genome‑wide association approach in a cohort of 1090 Crohn disease patients of European ancestry, reinforcing the gene’s involvement with key clinical phenotypes (PMID:25557950). Both studies contribute independent datasets that substantiate the association through statistical significance and haplotype analysis. This collective evidence forms the basis for a strong gene‑disease association assertion.

The clinical validity of the LY75–Crohn disease association has been assessed as strong. The Japanese study provided evidence from 51 probands with Crohn disease (PMID:27965521), while the European GWAS encompassed 1090 affected individuals (PMID:25557950). Although traditional familial segregation data are not available in these studies, the large sample sizes and replication across different populations provide robust support. The association is further bolstered by the identification of significant statistical relationships and phenotypic correlations in independent cohorts. The convergence of these findings supports the clinical utility of the genetic association in diagnostic decision‑making. Thus, the overall strength of the association is firmly placed in the strong category.

In terms of genetic evidence, the association is primarily based on SNP and haplotype analyses. Both studies underscore a complex inheritance pattern that is characteristic of multifactorial conditions rather than classical Mendelian traits. Although no specific coding variant in HGVS nomenclature was reported in the available data, the statistical associations derived from common variants serve as a proxy for genetic risk. The reported association involves markers that span the LY75 locus, indicating that common genetic variation rather than rare high‐penetrance mutations underpins the risk. These findings are congruent with the polygenic nature of Crohn disease. Overall, the genetic evidence supports a strong role for LY75 in conferring susceptibility to Crohn disease.

No precise coding variant in the required HGVS format (starting with “c.” and including a “(p…)” annotation) was detailed in the supplied evidence. As such, the variant list for this gene–disease association remains empty. The studies focused on SNP association analyses and did not report rare deleterious alterations that would translate directly into an HGVS coding change. Consequently, critical interpretation of the genetic data must rely on allelic association statistics rather than individual variant pathogenicity. Future investigations may reveal specific variants with coding consequences that further clarify the molecular basis of this association. For now, genetic evidence is best summarized in the context of association signals and haplotype associations.

Functional and experimental evidence for LY75 in the context of Crohn disease is limited based on the supplied data. No direct mechanistic studies or functional assays, such as expression analyses, knock‑out models, or rescue experiments, were provided that delineate the pathogenic mechanism. While the statistical associations are robust, they are not supported by experimental evidence demonstrating how LY75 alterations lead to disease pathology. Thus, although the genetic association is strong, the functional evidence is rated as limited. This gap highlights an opportunity for future research to investigate the biological role of LY75 in immune function and intestinal homeostasis. Integrating functional studies will be critical to fully elucidate the pathogenic mechanisms in Crohn disease.

In conclusion, the data from both the Japanese association study and the European GWAS provide compelling evidence for a strong association between LY75 and Crohn disease. The genetic evidence is based on large cohorts and robust statistical analyses, despite the absence of direct functional assessment. The lack of specific coding variants does not detract from the association derived from common allelic variations contributing to disease susceptibility. Overall, the integration of these findings supports the clinical utility of LY75 as a potential genetic marker for Crohn disease risk assessment. Clinicians and researchers should note that while diagnostic decision‑making can benefit from this association, further functional studies are warranted to detail the underlying mechanistic pathways. Key take‑home: LY75 represents a strong genetic association with Crohn disease, meriting its consideration in future diagnostic and commercial genetic panels.

References

• Disease markers • 2016 • Lymphocyte Antigen 75 Polymorphisms Are Associated with Disease Susceptibility and Phenotype in Japanese Patients with Inflammatory Bowel Disease PMID:27965521
• Gastroenterology • 2015 • Identification of risk loci for Crohn's disease phenotypes using a genome‑wide association study PMID:25557950

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