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The NDST3 gene has been investigated as a potential risk factor for bipolar disorder (PMID:29140583) as well as other neuropsychiatric conditions. Given its repeated evaluation in complex neuropsychiatric phenotypes, NDST3 remains of clinical interest for diagnostic decision‑making, despite conflicting reports in the literature.
In one targeted association study, researchers evaluated NDST3 in a Han Chinese cohort that included 1,344 bipolar disorder cases, 1,248 schizophrenia cases, 1,056 major depressive disorder cases, and 1,248 controls (PMID:29140583). This study found no significant differences in allelic or genotypic frequencies between cases and controls, suggesting that NDST3 may not play a major role in the causation of bipolar disorder in this population.
Conversely, a comprehensive GWAS review of schizophrenia and bipolar disorder identified NDST3 among several genes with genome‑wide significant associations (PMID:31096178). This systematic review, which integrated findings across 22 GWAS studies, provided supportive albeit modest evidence for the involvement of NDST3 in the genetic architecture underlying bipolar disorder. The review noted that, alongside genes like ANK3 and PLXNA2, NDST3 yielded association signals in independent samples.
Despite these observations, there remains a lack of segregation data and clear familial patterns, and no single causative variant has been definitively linked to bipolar disorder. The genetic evidence is further complicated by the inherent heterogeneity of psychiatric disorders. As such, while positive signals in GWAS meta‐analyses are encouraging, the absence of replication in a well‐powered case–control study underscores the limited overall strength of the genetic evidence.
No functional or experimental studies have been reported to delineate the mechanism of pathogenicity for NDST3 in bipolar disorder. The absence of cellular models, animal studies, or rescue experiments further limits the ability to confirm a biological basis for its involvement. Given these gaps, mechanistic insights remain speculative and do not bolster the genetic findings.
In summary, the available evidence presents a conflicting picture. One large association study found no significant link between NDST3 and bipolar disorder, whereas aggregated GWAS data suggest a nominal association within the context of a polygenic risk framework. Key take‑home message: Although NDST3 may contribute as one of many risk factors in bipolar disorder, its clinical utility for diagnostic or commercial applications remains limited until further replication and functional validation are achieved.
Gene–Disease AssociationLimitedOne targeted study with 1,344 bipolar disorder cases and corresponding controls (PMID:29140583) failed to find a significant association, while a GWAS review (PMID:31096178) provided modest evidence. Overall, the evidence is conflicting with no segregation data. Genetic EvidenceLimitedThe genetic evidence is based on common variant associations from GWAS reviews, lacking robust replication and clear segregation findings. The absence of a definitive causative variant in NDST3 further limits the strength of the genetic evidence. Functional EvidenceNoneNo functional assays, animal models, or rescue experiments have been reported to support a pathogenic mechanism involving NDST3 in bipolar disorder. |