SYNGR1 – Schizophrenia

SYNGR1 (HGNC:11498) has been investigated as a candidate susceptibility gene for schizophrenia through family-based and case–control studies across diverse populations. A novel nonsense variant was reported in a single South Indian pedigree, and in a cohort of 193 schizophrenia patients and 198 bipolar disorder patients five intragenic SNPs showed allelic association with schizophrenia (P = 0.028–0.00007) (PMID:16215643). Subsequent resequencing in 497 Han Chinese cases identified rare coding changes including c.665A>G (p.Asp222Gly) in one patient and an in‐frame insertion P202_T203insN in two patients absent from 507 controls (PMID:17049558). An Italian sample (274 cases, 335 controls) replicated association at rs715505 (P = 0.028) and uncovered additional rare variants, including p.Ser26Gly in six cases versus three controls (PMID:19641478), whereas a separate Han Chinese bipolar cohort (506 cases) showed no association (PMID:19665806).

Overall, the genetic evidence for SYNGR1 in schizophrenia is limited: only one family-based segregation, small to moderate case–control cohorts with inconsistent replication across ethnicities. Functional data consist of reduced postmortem SYNGR1 expression and in silico predictions that promoter SNPs (g.-673A>C, g.-318G>T) alter AP-1 and TGT3 binding but lack in vivo validation (PMID:17049558). No animal or cellular rescue studies have been published. Key take-home: current evidence is insufficient to support clinical genetic testing of SYNGR1 in schizophrenia without further robust association and mechanistic validation.

References

• Journal of human genetics • 2005 • SYNGR1 is associated with schizophrenia and bipolar disorder in southern India. PMID:16215643
• Journal of psychiatric research • 2007 • Identification of rare mutations of synaptogyrin 1 gene in patients with schizophrenia. PMID:17049558
• Psychiatry research • 2009 • No association between bipolar disorder and syngr1 or synapsin II polymorphisms in the Han Chinese population. PMID:19665806
• Psychiatric genetics • 2009 • Association study and mutational screening of SYNGR1 as a candidate susceptibility gene for schizophrenia. PMID:19641478

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