Minor allele C of rs12807809 polymorphism in NRGN contributes to the severity of psychosis in patients with Schizophrenia in South Indian population

Abstract

Schizophrenia (SCZ) as a severe and complex neuropsychiatric disorder and is characterized by positive symptoms, negative symptoms and cognitive dysfunctions. Genome-wide association studies (GWAS) have identified a strong association between the single nucleotide polymorphism (SNP) rs12807809 upstream of Neurogranin (NRGN) in a European population. This evidence prompted us to conduct an association study among 1005 schizophrenia cases and 1069 controls in a South Indian Population using TaqMan Allelic discrimination method. We observed an association of rs12807809 with SCZ in this study population. Allele frequencies and genotype frequencies of rs12807809 showed significant differences between cases and control subjects [p=0.0019; OR=0.69; 95% CI=(0.55-0.87)] and (p=0.0062). Further Genotype-Phenotype correlation revealed a moderate association of rs12807809 with flat affect (p=0.039) and Hallucinations (p=0.012). The ancestral non-risk C allele contributes to the severity of psychosis (p=0.039) in this population.

Association between NRGN gene polymorphism and resting-state hippocampal functional connectivity in schizophrenia

“…The genotypes of rs12807809 were confirmed by the Sanger sequencing technique. Large studies [3, 8, 30] found a low frequency of the CC genotype (less than 10% in both patients with SZ and HCs). In our study, the frequency of the CC genotype was 1.7% in patients with SZ and 12.1% in HCs.…”

“…In recent years, in genome-wide association studies, a single nucleotide polymorphism (SNP), rs12807809, in the NRGN gene was reportedly associated with SZ [2], and the T allele conferred a high risk for SZ. An association of rs12807809 with SZ was also found in 1005 SZ patients and 1069 controls in a South Indian population; further analysis found a moderate association of rs12807809 with flat affect and hallucinations [3]. In addition, an expression quantitative trait loci (eQTL) analysis provided evidence for an increased risk for SZ with rs12807809 at a molecular level [4].…”

Neurogranin: A Potential Biomarker of Neurological and Mental Diseases

“…A genome-wide association study identified a relationship between schizophrenia and the single nucleotide polymorphism of rs12807809 in the NRGN ( Stefansson et al, 2009 ). In recent years, several reports attempted to reveal the association between rs12807809 polymorphism and schizophrenia among different populations, but the results were controversial ( Li et al, 2010 ; Sudesh et al, 2017 ). A recent meta-analysis aiming to integrate the present studies on the 12807809 polymorphism showed a statistically significant association between schizophrenia and rs12807809 polymorphism in the overall population in the allelic model (odds ratio = 1.10, 95% confidence interval 1.04–1.17).…”