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Schizophrenia (SZ) is suggested to be a complex polygenetic disorder with high heritability. Genome-wide association studies have found that the rs1635, rs11038167, and rs10489202 polymorphisms are associated with SZ in Han Chinese. However, results of validation studies are inconsistent. This study aimed to test the association between the NKAPL rs1635, TSPAN18 rs11038167, and MPC2 rs10489202 polymorphisms and SZ in a Chinese population.
This study contained 700 unrelated SZ patients (300 Zhuang and 400 Han) and 700 gender- and age-matched controls (300 Zhuang and 400 Han). The polymorphisms in TSPAN18 (rs11038167), NKAPL (rs1635), and MPC2 (rs10489202) were genotyped using the Sequenom MassARRAY method. Statistical analyses were performed with PLINK program and SPSS l6.0 for Windows. STATA11.1 was used for meta-analysis.
No statistically significant difference was found in different allele and genotype frequencies of rs1635, rs11038167, and rs10489202 between SZ cases and controls of Zhuang and Han ethnicities and the total samples (all p>0.05). Further meta-analysis suggested that single-nucleotide polymorphism rs10489202 was significantly associated with SZ in a Han Chinese population (pOR=0.002).
Our case–control study failed to validate the significant association of NKAPL rs1635, TSPAN18 rs11038167, and MPC2 rs10489202 polymorphisms with SZ susceptibility in the southern Zhuang or Han Chinese population. However, meta-analysis showed a significant association between MPC2 variant rs10489202 and SZ susceptibility in Han Chinese.
Schizophrenia (SZ) is a common severe psychiatric disorder and a complex polygenic inherited disease that has not yet been fully interpreted. Heredity was proven to play an important role in the development of SZ. The association between the NOTCH4 gene rs3131296 polymorphism and SZ was reported to reach significance at the genome-wide level; therefore, it is necessary to replicate this association in other different populations.
To evaluate the association of the NOTCH4 gene rs3131296 polymorphism with the risk for SZ, and to explore whether a significant association could be replicated in different ethnic groups of China, we conducted this case–control study on 282 SZ cases (188 Han and 94 Zhuang) and 282 controls (188 Han and 94 Zhuang) among the Chinese Zhuang and Han populations.
The results showed no statistically significant difference in the genotype or allele frequencies of the NOTCH4 gene variant rs3131296 between SZ patients and healthy controls in either the Zhuang or Han samples (p > 0.05). In addition, no significant difference was found in genotype or allele frequencies of the NOTCH4 gene variant rs3131296 between cases and controls in the combined samples including Zhuang and Han samples.
Our study failed to replicate the significant association between the NOTCH4 gene rs3131296 polymorphism and the risk for SZ.
Schizophrenia (SCZ) and bipolar disorder (BD) are common psychotic disorders, which show some overlaps in genetic aetiology. Researchers have conducted a number of studies to investigate the relationship between SCZ and the 1354C/T genetic polymorphism of 5-hydroxytryptamine receptor 2A (HTR2A–1354C/T), as well as the associations between BD and the HTR2A–1354C/T polymorphism. However, the results were conflicting. To provide a more robust estimate about the effects of the HTR2A–1354C/T polymorphism on the risk of these two psychotic disorders, we performed this meta-analysis.
We used the pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) to investigate the relationships between SCZ and the 1354C/T polymorphism of HTR2A, as well as the associations between BD and HTR2A–1354C/T. Publication bias was tested by Begg's test and inverted funnel plot, and heterogeneity was checked by Cochran's Q statistic and the inconsistency index (I2).
Eight studies were concerned with SCZ, analysing a cumulative total of 2953 cases and 3153 controls; six papers studied BD, using a total of 923 cases and 928 controls. There was no significant association found between HTR2A–1354C/T and SCZ in the overall population (T allele vs. C allele, OR = 1.035, 95% CI 0.912–1.175, p = 0.596) or in the subgroups Caucasian population and Asian population. Moreover, there was no significant association between the HTR2A–1354C/T polymorphism and BD in the overall population (T allele vs. C allele, OR = 1.038, 95% CI = 0.607–1.772, p = 0.892).
On the basis of these results, the HTR2A–1354C/T polymorphism is unlikely to be a risk factor for SCZ and BD.
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