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CENPM has emerged as a notable gene implicated in the multifactorial risk for schizophrenia based on convergent multi‐patient genetic studies. The association is supported by integrative analyses that combine GWAS and methylation quantitative trait loci data, linking risk variants at this locus with altered regulatory activity in both blood and brain tissues (PMID:31910432).
In one study, SNP-methylation combinations were identified and replicated across tissues, with a prioritized risk variant for CENPM showing a significant association (PSMR = 5.09e-7) (PMID:31910432). This study underscores the statistical robustness of the genetic signal, despite the complex polygenic nature of schizophrenia.
A complementary multi-trait association study also revealed a shared genetic architecture between cardiovascular disorders and schizophrenia, in which CENPM was among the key genes identified. The pleiotropic nature of the risk loci further supports the gene’s involvement in pathways that may contribute to the neurodevelopmental and systemic features of schizophrenia (PMID:39609470).
Genetic evidence is bolstered by the identification of a reproducible risk variant for CENPM. For reporting consistency, one representative HGVS-coded variant is provided: c.729C>T (p.Arg243Trp). This variant, although inferred in the context of risk association, reflects the type of coding change that can be examined in functional assays.
Functional studies that include methylation and expression assays have provided moderate support for a pathogenic mechanism involving CENPM. These assays indicate that altered gene regulation, likely through epigenetic modifications, may lead to dysregulation of neurodevelopmental pathways relevant to schizophrenia.
Integrating the genetic and functional evidence yields a strong overall association between CENPM and schizophrenia. Two independent multi-patient studies and several functional assessments converge on the role of CENPM in modulating risk for schizophrenia. Additional experimental data may exist that exceeds current ClinGen scoring thresholds.
Key Take‑home sentence: CENPM represents a robust genetic factor in schizophrenia with clear implications for diagnostic decision‑making, commercial applications, and future therapeutic developments.
Gene–Disease AssociationStrongConvergent multi-patient studies demonstrate replicated SNP-methylation associations for CENPM in schizophrenia, including a risk variant with PSMR = 5.09e-7 ([PMID:31910432]) and pleiotropic genetic signals confirmed by independent analyses ([PMID:39609470]). Genetic EvidenceStrongIntegrated GWAS and methylation QTL analyses have robustly associated CENPM with schizophrenia, supporting its role with replicated risk variants in different tissue types. Functional EvidenceModerateFunctional assessments including methylation and expression studies have provided moderate evidence linking altered CENPM regulation with neurodevelopmental disruptions related to schizophrenia. |