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Recent cross‑phenotype genome‑wide association studies (GWAS) have identified a significant shared genetic susceptibility between systemic sclerosis and primary biliary cholangitis, with CFAP263 emerging as one of the prioritized candidate causal genes for primary biliary cholangitis (PMID:39676709) (PMID:39006426). This association is based on large‐scale meta‑analyses that evaluated thousands of patients, detecting a robust genetic correlation (rg = 0.84, p = 1.7×10^-6) and identifying 44 non‑HLA loci with genome‑wide significance.
The genetic evidence supporting the involvement of CFAP263 comes from two independent analyses. Both studies integrated locus‑based evaluation and Bayesian colocalization analyses, ultimately prioritizing CFAP263 along with other candidate genes. Although traditional case‑based segregation data or reports of specific familial variants were not available, the population‑based aggregation of risk variants offers compelling statistical support for the gene–disease association (PMID:39676709) (PMID:39006426).
Importantly, the nature of the findings reflects a complex, multifactorial inheritance pattern rather than a classic Mendelian mode. No single or segregating HGVS‑reported variant has been implicated; instead, the association arises from common genetic variations that cumulatively contribute to disease risk. Thus, while individual variant specifics were not delineated, the overall genetic signal remains strong.
The available evidence does not provide traditional segregation data with affected relatives in family studies; rather, the conclusions are drawn from robust cross‑phenotype statistical associations in large patient cohorts. Consequently, explicit HGVS variant descriptions were not reported for CFAP263 in these analyses.
Functional or experimental assessments directly interrogating CFAP263’s role in primary biliary cholangitis are limited in the supplied data. While the studies suggest a plausible pathophysiological contribution through integrative genomic approaches, no targeted cellular or animal models, expression assays, or rescue experiments were detailed. This leaves a gap in the direct experimental confirmation of the gene’s mechanistic role.
In summary, the converging genetic evidence from independent and robust GWAS meta‑analyses strongly supports an association between CFAP263 and primary biliary cholangitis. Although functional validation is currently limited, the replication of genetic signals in diverse cohorts underscores CFAP263’s potential clinical utility as a diagnostic marker and candidate for future therapeutic investigations.
Gene–Disease AssociationStrongCFAP263 was prioritized by two independent cross‑phenotype GWAS meta‑analyses demonstrating robust statistical association (rg = 0.84, p = 1.7×10^-6) and colocalization evidence (PMID:39676709) (PMID:39006426). Genetic EvidenceStrongMultiple large‑scale analyses identified CFAP263 among 44 non‑HLA loci with genome‑wide significance, supporting its involvement in complex disease risk. Functional EvidenceLimitedNo direct functional assays or model systems were detailed to validate CFAP263’s mechanistic role in primary biliary cholangitis. |