Neuregulin 3does not confer risk for schizophrenia and smooth pursuit eye movement abnormality in a Korean population

Abstract

Located on chromosome 10q22-q23, the human neuregulin3 (NRG3) is considered to be a strong positional and functional candidate gene for schizophrenia pathogenesis. Several case-control studies examining the association of polymorphisms in NRG3 with schizophrenia and/or related traits such as delusion have been reported recently in cohorts of Han Chinese, Ashkenazi Jews, Australians and white Americans of Western European ancestry. Thus, this study aimed to comprehensively investigate the association of NRG3 genetic variations with the risk of schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Using TaqMan assay, six single-nucleotide polymorphisms (SNPs) in the intronic region of NRG3 were genotyped and two major haplotypes were identified in 435 patients with schizophrenia as cases and 393 unrelated healthy individuals as controls. A total of 113 schizophrenia patients underwent an eye tracking task, and degree of SPEM abnormality was measured using the logarithmic values of the signal/noise (Ln S/N) ratio. Differences in frequency distributions were analyzed using logistic and regression models following various modes of genetic inheritance and controlling for age and sex as covariates. Subsequent analysis revealed that the frequency distributions of NRG3 polymorphisms and haplotypes were similar between schizophrenia patients and healthy controls of Korean ethnicity. Furthermore, no significant differences were observed between the genetic variants tested for SPEM abnormality. By elucidating a lack of association in a Korean population, findings from this study may contribute to the understanding of the genetic etiology focusing on the role of NRG3 in schizophrenia pathogenesis.

BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia

“…A study of NRG1 genotypes with eye movement deficits in 113 patients with schizophrenia and 106 age-matched healthy controls found no relationship between NRG1 genotype (SNP8NRG222662, SNP8NRG243177) and ASEM or SPEM task performance ( Haraldsson et al, 2010 ). Consistent with Haraldsson’s study, two studies in Korea also found no associations between NRG1 (rs35753505G, rs4623364G; rs6994992T rs3924999A) and ASEM or SPEM abnormality ( Pasaje et al, 2011 ; Kim et al, 2012 ). However, the result in healthy subjects showed interaction between NRG1 and eye movement deficits.…”

Neuregulin 3 and its roles in schizophrenia risk and presentation

“…These SNPs however were not in LD with any other reported SNPs in terms of r 2 (see Figure 5 for pairwise LD information in Caucasians on these and all other SNPs mentioned in this review and shown in Figure 1). Two more positive studies reported an association between rs10883866 and/or correlated SNPs and schizophrenia, [Kao et al, 2010] and [Morar et al, 2011], There have also been three negative studies [Zhang et al, 2013; Pasaje et al, 2011; Chen et al, 2009] and the genomic region does not show significant signals in the biggest genome wide association study for schizophrenia to date of 150,00 samples [Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014]. Therefore, the involvement of these variants with risk for schizophrenia remains in question.…”