TSNARE1 polymorphisms are associated with schizophrenia susceptibility in Han Chinese.

Abstract

t-SNARE domain containing 1 gene (TSNARE1) is located at human chromosome 8q24.3, and may play a crucial role in intracellular protein transport and synaptic transmission. Recently, a large-scale meta-analysis of genome-wide association study dataset identified that rs10098073 and rs4129585, two single nucleotide polymorphisms (SNPs) within TSNARE1, were closely associated with the risk of schizophrenia in Caucasians. However, this finding has not been validated in other populations or ethnic groups thus far. In the current study, we conducted a case-control study to confirm the association of these two SNPs with the schizophrenia risk in a Han Chinese population comprising 440 schizophrenia patients and 450 control subjects. According to the genotype data of Han Chinese from Beijing in 1,000 Genomes Project database, rs10098073 and rs4129585 were located in one haplotype block and were in almost complete linkage disequilibrium (D' = 1, r (2) ≥ 0.952). Therefore, only rs10098073 was selected for the subsequent analysis. We showed for the first time that the minor allele (A) of rs10098073 was associated with a reduced risk of schizophrenia (OR = 0.753; 95 % CI 0.613-0.924; P = 0.007). Furthermore, we found that the A allele of rs10098073 reduced the schizophrenia risk through a recessive manner (A/A vs. A/C + C/C, OR = 0.563; 95 % CI 0.357-0.89; P = 0.013, P Bonferroni corrected = 0.026) rather than a dominant manner (A/A + A/C vs. C/C, OR = 0.762; 95 % CI 0.586-0.992; P = 0.043, P Bonferroni corrected = 0.086). Taken together, these findings demonstrate a significant association between TSNARE1 polymorphisms and schizophrenia risk in a Han Chinese population, suggesting TSNARE1 may represent a susceptibility gene for this disease.