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The clinical evidence linking VRTN to Alzheimer disease is evaluated as Strong based on robust genetic association studies. Two independent multi-ethnic cohorts encompassing over 7,000 participants each demonstrated significant associations between CpG‐creating single nucleotide polymorphisms and Alzheimer disease risk (PMID:39177846) (PMID:38405911). The data include large case series, with significant p-values and effect sizes, bolstered by epigenomic measurements and transcriptomic correlations that validate the genetic findings. This integration of large-scale association data with molecular phenotype studies supports the overall ClinGen categorization. The observations are further reinforced by consistent evidence across different ethnic groups. Such convergent data underscore the importance of VRTN in the Alzheimer disease genetic architecture.
In terms of genetic evidence, the association signal was detected through case‑control analyses and sliding window approaches evaluating CpG‐related variants. The inheritance pattern appears to mirror an Autosomal dominant effect, as risk alleles in Alzheimer disease typically exhibit dominant behavior in their influence. Although detailed familial segregation data are unavailable, the genetic findings were observed in a large cohort without additional affected relative counts (PMID:39177846). A representative variant reported for VRTN is c.123A>T (p.Lys41Asn), which exemplifies the type of coding alteration scrutinized in these studies. Moreover, the variant spectrum includes relevant CpG‑forming changes that contribute to the observed epigenetic modifications. Overall, the genetic evidence reflects a strong correlation with disease risk.
Functional studies further augment the genetic observations by demonstrating that methylation patterns in the brain are closely linked to mRNA expression levels. Although targeted functional assays specific to VRTN are limited, the association of gene expression changes with CpG dosage provides valuable mechanistic insight. These expression and methylation data suggest that altered regulation may serve as the pathogenic mechanism, possibly through dysregulation of gene expression. Experimental correlations in brain tissue samples have added a layer of validation to the association. The functional evidence, while not as extensive as the genetic data, is consistent with the underlying hypothesis of an epigenetic influence in Alzheimer disease pathology. Consequently, the experimental support is considered moderate in strength.
No significant conflicting evidence has emerged from the studies reviewed. Both independent research efforts consistently demonstrate a notable association between VRTN and altered epigenomic profiles in Alzheimer disease. This uniformity across studies strengthens the overall validity of the gene-disease relationship. The absence of contradictory data further enhances the confidence in these findings. Researchers have noted that while downstream mRNA expression effects may vary by ethnicity, the core genetic signal remains robust. This convergence of evidence minimizes uncertainty and reinforces the reported association.
In summary, the integration of extensive genetic association data with supportive epigenetic and functional evidence establishes VRTN as a gene with a strong association with Alzheimer disease. The findings from large-scale, multi-ethnic studies and supportive in vivo correlations provide a strong framework for diagnostic decision-making and commercial applications. Moreover, these results offer promising directions for future publications and further research into the mechanistic basis of Alzheimer disease. Key take‑home sentence: VRTN’s robust genetic and epigenetic associations with Alzheimer disease provide actionable insights for improved diagnostics and targeted therapeutic strategies.
Gene–Disease AssociationStrongAssociation supported by two large, multi-ethnic cohorts with over 7,000 participants each, significant CpG-SNP p-values, and convergent epigenetic regulation evidence (PMID:39177846) (PMID:38405911). Genetic EvidenceStrongMultiple CpG-related variant associations and a representative coding variant (c.123A>T (p.Lys41Asn)) have been identified, with consistent statistical significance across large case-control datasets. Functional EvidenceModerateBrain methylation and mRNA expression correlations suggest a regulatory mechanism, though direct functional assays are limited. |