Abstract
Aims: We aimed to explore whether RELN contributes to the vulnerability and severity of clinical symptoms of schizophrenia (SZ) in a Chinese population.Methods: The following were conducted in an adult Han Chinese population from southern China: case–control association analyses of 30 representative single nucleotide polymorphisms (SNPs) that were screened according to specific programs based on bioinformatics tools and former research and quantitative trait locus analyses with SNPs and psychiatric symptoms evaluated with the positive and negative symptoms scale.Results: A 4-SNP haplotype consisting of rs362814, rs39339, rs540058, and rs661575 was found to be significantly associated with SZ even after Bonferroni correction (χ2 = 29.024, p = 6.42E-04, pBonf = 0.017), and the T-C-T-C haplotype was a protective factor for SZ (OR = 0.050, 95% CI = 0.004–0.705). Moreover, the 4-SNP haplotype showed a significant association with G16 (active social avoidance) after false discovery rate correction (χ2 = 28.620, p = 1.697E-04, pFDR = 0.025). In addition, P7 (hostility) was related to the haplotype comprising rs2229864, rs2535764, and rs262355 (χ2 = 31.424, p = 2.103E-05, padjustment = 0.019) in quantitative trait loci analyses.Conclusion: Overall, this study showed several positive associations between RELN and SZ, as well as psychiatric symptoms, which not only supports the proposition that RELN is a susceptibility gene for SZ but also provides information on a genotype-phenotype correlation for SZ in a Chinese population.
Highlights
Schizophrenia (SZ, Online Mendelian Inheritance in Man [OMIM] 181500) is a common and serious psychiatric disorder with a lifetime prevalence estimate of 4.0 (1.6–12.1) per 1,000 individuals (Esan et al, 2012)
No single nucleotide polymorphisms (SNPs) deviation from Hardy-Weinberg equilibrium (HWE) was found in the controls (Table 1)
We performed qualitative and quantitative trait association analyses in a Han Chinese population from southern China to verify that RELN was a susceptibility gene for SZ
Summary
Schizophrenia (SZ, Online Mendelian Inheritance in Man [OMIM] 181500) is a common and serious psychiatric disorder with a lifetime prevalence estimate of 4.0 (1.6–12.1) per 1,000 individuals (Esan et al, 2012). Low level or dysfunctional of reelin protein may cause deficits in neuronal development and cognitive function in adults and may play pathogenic roles in neuropsychiatric illnesses, such as SZ. This proposition was further supported by anatomical and in vivo studies that included the reeler mice and the heterozygous reeler mouse (HRM) model (Hill et al, 2006; Qiu et al, 2006; Tueting et al, 2006). The results remain controversial (Tost and Weinberger, 2011; Li et al, 2013; Bocharova et al, 2017)
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