1Nat. Genet. 2011 Dec 43: 1228-31
TitleGenome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2.
AbstractTo identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P(combined) = 4.76 10(-11), odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, P(combined) = 6.91 10(-12), OR = 0.78; rs2142731 in an intron of PGBD1, P(combined) = 5.14 10(-10), OR = 0.79) and 11p11.2 (rs11038167 near the 5' UTR of TSPAN18, P(combined) = 1.09 10(-11), OR = 1.29; rs11038172, P(combined) = 7.21 10(-10), OR = 1.25; rs835784, P(combined) = 2.73 10(-11), OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia.
SCZ Keywordsschizophrenia
2PLoS ONE 2013 -1 8: e58785
TitleReplication study confirms link between TSPAN18 mutation and schizophrenia in Han Chinese.
Abstractschizophrenia (SCZ) is a severe psychiatric disorder associated with many different risk factors, both genetic and environmental. A recent genome-wide association study (GWAS) of Han Chinese identified three single-nucleotide polymorphisms (SNPs rs11038167, rs11038172, and rs835784) in the tetraspanins gene TSPAN18 as possible susceptibility loci for schizophrenia. Hoping to validate these findings, we conducted a case-control study of Han Chinese with 1093 schizophrenia cases and 1022 healthy controls. Using the LDR-PCR method to genotype polymorphisms in TSPAN18, we found no significant differences (P>0.05) between patients and controls in either the allele or genotype frequency of the SNPs rs11038167 and rs11038172. We did find, however, that the frequency of the 'A' allele of SNP rs835784 is significantly higher in patients than in controls. We further observed a significant association (OR=?1.197, 95%CI=?1.047-1.369) between risk for SCZ and this 'A' allele. These results confirm the significant association, in Han Chinese populations, of increased SCZ risk and the variant of the TSPAN18 gene containing the 'A' allele of SNP rs835784.
SCZ Keywordsschizophrenia
3Int J Mol Sci 2015 -1 16: 11864-72
TitleLack of Association between the TSPAN18 Gene and Schizophrenia Based on New Data from Han Chinese and a Meta-Analysis.
AbstractTetraspanin-18 (TSPAN18) potentially plays a role in the calcium signaling that is associated with dopamine-induced cortical neuron apoptosis and is considered to be an important mechanism in the pathogenesis of schizophrenia (SCZ). Furthermore, a genome-wide association study (GWAS) identified TSPAN18 as a possible susceptibility gene for SCZ. To validate these findings and reveal the effects of different inheritance models, seven single nucleotide polymorphisms (SNPs) of the TSPAN18 gene were analyzed in 443 patients with SCZ and 628 controls of Han Chinese descent via the SNPscan method. Single SNP, genotype, and association analyses with different models (i.e., additive, dominant, and recessive models) were performed, and the published datasets (2062 cases and 2053 controls) were combined with our results to determine the inheritance effects of the SNPs on SCZ. We observed genotypes and allele distributions of TSPAN18 gene did not show any significant associations in the Han Chinese population based on our experimental and meta-analytical results. Our findings indicate that the TSPAN18 gene is unlikely to be a major susceptibility gene for schizophrenia in Han Chinese.
SCZ Keywordsschizophrenia
4Psychiatry Res 2016 May 241: 263-266
TitleStudy of the tetraspanin 18 association with schizophrenia in a Han Chinese population.
AbstractA genome-wide association study of Han Chinese samples identified three single-nucleotide polymorphisms in the tetraspanin 18 (TSPAN18) gene to be associated with schizophrenia. However, the replication of the TSPAN18 association was inconsistent across studies. To explore the possible reason for poor replication, we conducted a case-control study to validate the TSPAN18 finding in an independent Chinese sample. The frequency of rs11038167 minor allele (A) was significantly higher only in female patients with thought disorder. Our result suggested that the TSPAN18 gene may be involved in the development of psychotic symptoms and contribute to clinical heterogeneity of schizophrenia.
SCZ Keywordsschizophrenia