Association study of Neuregulin-1 gene polymorphisms in a north Indian schizophrenia sample

Department of Genetics, University of Delhi South campus, Benito Juarez Road, New Delhi - 110 021, India
Schizophrenia Research (Impact Factor: 3.92). 01/2013; 144(1-3). DOI: 10.1016/j.schres.2012.12.017
Source: PubMed


Neuregulin-1 (NRG1) gene polymorphisms have been proposed as risk factors for several common disorders. Associations with cognitive variation have also been tested. With regard to schizophrenia (SZ) risk, studies of Caucasian ancestry samples indicate associations more consistently than East Asian samples, suggesting heterogeneity. To exploit the differences in linkage disequilibrium (LD) structure across ethnic groups, we conducted a SZ case-control study (that included cognitive evaluations) in a sample from the north Indian population.

NRG1 variants (n=35 SNPs, three microsatellite markers) were initially analyzed among cases (DSM IV criteria, n=1007) and controls (n=1019, drawn from two groups) who were drawn from the same geographical region in North India. Nominally significant associations with SZ were next analyzed in relation to neurocognitive measures estimated with a computerized neurocognitive battery in a subset of the sample (n=116 cases, n=170 controls).

Three variants and one microsatellite showed allelic association with SZ (rs35753505, rs4733263, rs6994992, and microsatellite 420M9-1395, p≤0.05 uncorrected for multiple comparisons). A six marker haplotype 221121 (rs35753505-rs6994992-rs1354336-rs10093107-rs3924999-rs11780123) showed (p=0.0004) association after Bonferroni corrections. Regression analyses with the neurocognitive measures showed nominal (uncorrected) associations with emotion processing and attention at rs35753505 and rs6994992, respectively.

Suggestive associations with SZ and SZ-related neurocognitive measures were detected with two SNPs from the NRG1 promoter region in a north Indian cohort. The functional role of the alleles merits further investigation.

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Available from: Prachi Kukshal
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    • "Overall, dozens of SNPs of NRG1 have been associated with schizophrenia, both at 5 0 (Kukshal et al. 2013; Benzel et al. 2007; Corvin et al. 2004; Hall et al. 2004; Petryshen et al. 2005; Stefansson et al. 2002; Zhao et al. 2004) and 3 0 regions (Bakker et al. 2004; Benzel et al. 2007; Lachman et al. 2006; Li et al. 2004; Petryshen et al. 2005). Recently, genome-wide association studies (GWAS) for schizophrenia have also reported a nominal association between several SNPs in NRG1 gene and schizophrenia, with p values spanning from 1.59 9 10 -5 for rs4316112 to 1.38 9 10 -3 for rs10095694 (Athanasiu et al. 2010; Shi et al. 2009). "
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    • "We attempted to examine the effect of DTNBP1 (rs1011313) and NRG1 (rs35753505) polymorphisms on brain morphometry in patients with schizophrenia and healthy subjects recruited from South India. From amongst several SNPs of the NRG1 and DTNBP1genes that have been reported to be significantly associated with schizophrenia (Funke et al., 2004; Yang, 2012), we chose the, above-mentioned SNPs of DTNBP1 and NRG1 genes, as they have been shown by previous haplotype analysis and association studies to be core markers of schizophrenia (Bray et al., 2005; Kukshal et al., 2013; Nawaz et al., 2013; Pae et al., 2008; Prata et al., 2009). Surprisingly, however, no previous study has examined the relationship between the above SNPs and brain volumes. "
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