Association of haplotypes spanning PDZ-GEF2, LOC728637 and ACSL6 with schizophrenia in Han Chinese

Kunming Institute of Zoology, CAS, China.
Journal of Medical Genetics (Impact Factor: 6.34). 09/2008; 45(12):818-26. DOI: 10.1136/jmg.2008.060657
Source: PubMed


Schizophrenia is a complex genetic disorder caused by multiple genetic and environmental factors. Several lines of linkage and association studies have repeatedly suggested that the chromosome 5q22-33 region is implicated in the aetiology of schizophrenia. However, most of the previous studies on the linkage of 5q22-33 with schizophrenia were from European populations, and it was not well characterised in other populations.
We analysed eight single nucleotide polymorphisms (SNPs) located in the 5q23.3 region in a cohort of 506 schizophrenia patients and 672 control subjects from south western China. Single marker association, haplotypic association, sex-specific association and molecular evolutionary analysis were performed.
Single marker analysis indicated that SNP5 (rs1355095) in LOC728637 is associated with schizophrenia. When males and females were analysed separately, SNP4 (rs31251) in PDZ-GEF2 is associated with schizophrenia in females. Further analysis using haplotypes demonstrated that a haplotype block spanning PDZ-GEF2, LOC728637 and ACSL6 is highly associated with schizophrenia and several haplotypes in this haploblock have about twofold to 10-fold increase in the affected subjects. In addition, molecular evolutionary analysis suggests that PDZ-GEF2 has undergone adaptive evolution due to Darwinian positive selection in the human lineage.
Our data provide evidence of the association of 5q22-33 with schizophrenia in Han Chinese. This chromosomal region is likely responsible for genetic susceptibility to schizophrenia, supporting previous data from European patients. In addition, our evolutionary analysis is consistent with the hypothesis that genes contributing to schizophrenia are likely under positive selection during human evolution.

Download full-text


Available from: Bing Su
  • Source
    • "This sample has been reported previously [22]–[25], and no population stratification was observed [3] when evaluated with the STRUCTURE software [26]. Genotyping of Yunnan sample was performed using SNaPShot as previously described [27], and the genotyping success rate was over than 99%. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent genetic analyses have implicated several candidate susceptibility variants for schizophrenia. The single nucleotide polymorphism (SNP) rs7294919 is likely a schizophrenia-susceptibility variant according to its significant association with hippocampal volume, hippocampus function, and cognitive performance as well as the nominal association with schizophrenia. However, all previous analyses were conducted only in Europeans, and whether rs7294919 is associated with schizophrenia in other populations are yet to be tested. Here, we conducted a case-control analysis of rs7294919 with schizophrenia in six independent Chinese (N = 3) and Japanese (N = 3) samples, including a total of 7,352 cases and 10,824 controls. The results of our association analysis were not able to confirm the association of rs7294919 with schizophrenia (p = 0.51 in total samples, odds ratio = 1.02 for allele[C]). The absence of rs7294919's association in Chinese and Japanese suggest a potential genetic heterogeneity in the susceptibility of schizophrenia on this locus and also demonstrate the difficulties in replicating associations of schizophrenia across different ethnic populations.
    Full-text · Article · Nov 2013 · PLoS ONE
  • Source
    • "The DNA samples of the cases and controls were randomly distributed in the case-control DNA plates. All selected SNPs were genotyped by SNaPShot as described in our previous study (Luo et al. 2008). In brief, genomic fragments which contained selected SNPs were amplified by PCR with a total volume of 25 μL (including 10 ng of genomic DNA) in 96-well plates. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous research on gene expression analysis and association tests have suggested that RELN is a risk gene for schizophrenia in world populations. Based on the reported down-regulation of RELN in schizophrenia patients compared with normal subjects, we speculated that variants in the RELN promoter region may confer risk for schizophrenia. In this study, we investigated the associations of three SNPs in the promoter region of RELN with schizophrenia in a case-control sample from southwestern China (940 cases and 1 369 controls). The results suggested that none of the SNPs showed significant associations in our sample, indicating the risk variants for schizophrenia in RELN may not be located in the promoter region. We also performed meta-analysis by combining our data with previously reported data on the Chinese population with a total sample size of 2 843 individuals, and the result remained non-significant. Collectively, our results suggested variants in the RELN promoter may not harbor risk SNPs associated with schizophrenia in the Chinese population.
    Full-text · Article · Oct 2011 · Zoological Research
  • Source
    • "DNA samples of the cases and controls were randomly distributed in our case-control DNA plates. All the selected SNPs were genotyped by the SNaPShot method as described in our previous study (Luo et al. 2008). In brief, the genomic fragments which contain the selected SNPs were amplifi ed by polymerase chain reaction (PCR) with a total volume of 25 μ l (including 10 ng of genomic DNA) in 96-well plates. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Objectives. Several lines of evidence have shown that both RELN mRNA and protein are possibly down-regulated in the brain of schizophrenia patients. Recent association studies in European populations suggested RELN as a risk gene for schizophrenia. In this study, we test if RELN contributes to the risk of schizophrenia in Chinese population. Methods. We conducted case-control association analysis of 19 representative single nucleotide polymorphisms (SNPs) spanning the entire region of RELN in two independent Han Chinese samples from southwestern China (the Kunming sample and the Yuxi sample). Results. We identified six SNPs significantly associated with schizophrenia in the Kunming sample and four of them remained significant in the combined samples (the P values range from 0.006 to 4.0 ? 10(?5)). Haplotype analysis also suggested significant associations for the haplotypes incorporating the six significant SNPs (global P < 1.0 ? 10(?5)). Additionally, we also observed several other haplotypes (defined by a different set of SNPs) significantly associated with schizophrenia in the Kunming sample. However, the reported association of rs7341475 in Ashkenazi Jews was not significant in Han Chinese. Conclusions: Our findings demonstrate that RELN is a susceptibility gene for schizophrenia in Chinese population, and it is likely a common risk gene for schizophrenia in major populations worldwide.
    Full-text · Article · Jul 2011 · The World Journal of Biological Psychiatry
Show more