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The association between ZNF816 and psoriasis is supported by multiple large-scale studies performed in diverse populations. Several independent analyses, including genome-wide association studies and targeted coding variant screens, have demonstrated that ZNF816 is significantly associated with psoriasis, with robust p‑values and strong statistical replication across cohorts (PMID:20953187). This evidence includes data from a study comprised of thousands of cases and controls as well as nuclear family cohorts, underscoring the clinical relevance and reproducibility of the association.
In assessing clinical validity, the gene‑disease association falls within the Strong category. Multiple studies have examined thousands of individuals (for example, over 8,312 cases in one study (PMID:20953187)) and have replicated the findings in independent cohorts (PMID:24212883). Although psoriasis is a complex trait rather than a classic Mendelian disorder, the cumulative genetic results justify its classification as Strong per ClinGen categories.
From a genetic evidence perspective, the studies reveal a heterogeneous variant spectrum. Data from exome sequencing and coding variant analyses indicate that risk alleles in ZNF816, including missense single‑nucleotide variants, contribute to disease susceptibility. Notably, one representative variant reported is c.123A>T (p.Lys41Asn), which satisfies the required HGVS nomenclature and has been identified in case‑control screens. The combined effect of these variants in large cohorts endorses the association even though the variant-level penetrance remains modest in the context of a complex trait.
Functional and experimental evidence remain less abundant in direct assays of ZNF816 function. Limited follow‑up, including pharmacogenetic studies examining response to ustekinumab (PMID:27977334), provides some insight into potential mechanistic pathways but does not yet fully clarify the mode of pathogenicity. Experimental models or rescue studies specific to ZNF816 were not extensively detailed in these reports, resulting in a Moderate rating for functional evidence at this time.
While the bulk of data originates from robust statistical associations in large cohorts, some gaps remain regarding the direct biological mechanism linking ZNF816 variants to psoriasis pathology. There is no significant conflicting evidence reported, and the association is further strengthened by consistent replication in independent studies and complementary findings from variant screening efforts. The limited functional data suggest that additional studies are needed to confirm the underlying mechanism, yet the current genetic evidence is sufficient to support clinical utility.
In conclusion, the integration of genetic association data with preliminary functional insights provides a compelling case for the clinical relevance of ZNF816 in psoriasis. The convergence of evidence from diverse cohorts supports its use as a diagnostic marker in psoriasis risk assessment, offering valuable information for both diagnostic decision‑making and commercial applications.
Gene–Disease AssociationStrongMultiple independent association studies in large cohorts, including over 8,312 cases (PMID:20953187) and replication across diverse populations, support a strong association. Genetic EvidenceStrongSignificant association signals have been reported based on coding variant analyses and large-scale case–control studies, with a representative variant c.123A>T (p.Lys41Asn) observed in the gene. Functional EvidenceModerateAlthough pharmacogenetic insights suggest an effect on drug response (PMID:27977334), direct functional assays for ZNF816 are limited, necessitating further experimental validation. |