Association study of RELN polymorphisms with schizophrenia in Han Chinese population

Schizophrenia (SZ) is a common and complex psychiatric disorder with a strong genetic component. Previous research suggests that mutations altering genes in neurodevelopmental pathways contribute to SZ. Reelin gene (RELN) maps to chromosome 7q22.1, the encoded protein plays a pivotal role in guiding neuronal migration, lamination and connection during embryonic brain development. Several reports had indicated that reduced RELN expression is associated with human mental illnesses such as SZ, mood disorders and autism. In this study, case–control association analyses were performed in the Han Chinese population to determine if the RELN gene is a susceptibility gene for SZ. Thirty-seven single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was found between rs12705169 and SZ (p = 0.001). Moreover, the haplotypes constructed from five SNPs showed significant differences between cases and controls (p = 0.041). When subjects were divided by gender, rs12705169 remained significant difference only in females (OR = 0.24, 95%CI = 0.14–0.40 for CC and OR = 0.40, 95%CI = 0.27–0.58 for AC), both in the allele and genotype (p = 0.0001 for both). This study describes a positive association between RELN and SZ in the Han Chinese population, and provides genetic evidence to support the gender difference of SZ.

Research Highlights
► In this study, case–control association analyses were performed in the Chinese Han population to determine if the RELN gene is a susceptibility gene for SZ.
► A significant association was found between rs12705169 and SZ (permutation p = 0.001).
► The haplotypes constructed from five SNPs showed significant differences between cases and controls (permutation p = 0.006).
► When subjects were divided by gender, rs12705169 remained significant difference only in females, both in the allele and genotype (permutation p = 0.0001 for both).
► Only patients with paranoid SZ were included