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Evidence for association between Disrupted-in-Schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based association study.

Zheng F, Wang L, Jia M, Yue W, Ruan Y, Lu T, Liu J, Li J, Zhang D - Behav Brain Funct (2011)

Bottom Line: However, the results were not replicated in Korean population.After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant.These results were still significant after using the permutation method to obtain empirical p values.

View Article: PubMed Central - HTML - PubMed

Affiliation: Key Laboratory for Mental Health, Ministry of Health, Beijing, PR China.

ABSTRACT

Background: Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism.

Methods: We genotyped seven tag single nucleotide polymorphisms (SNPs) in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software.

Results: We found three SNPs showed significant associations with autism (rs4366301: G>C, Z=2.872, p=0.004; rs11585959: T>C, Z=2.199, p=0.028; rs6668845: A>G, Z=2.326, p=0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values.

Conclusions: Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism.

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Related in: MedlinePlus

DISC1 gene locus and linkage disequilibrium (LD) structure. (A) A diagram showing the exonic structure of DISC1 gene (black). The single nucleotide polymorphisms (SNPs) used in this study are shown in relation to the exons. (B)The linkage disequilibrium (LD) structure of the DISC1 region in the total autism samples according to Haploview (solid spine of LD, D'> 0.7). Markers with LD (D' < 1 and LOD > 2) are shown in red through pink (color intensity decreases with decreasing D' value). Regions of low LD (D' < 1 and LOD < 2) are shown in white. Two blocks were generated by Haploview.
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Figure 1: DISC1 gene locus and linkage disequilibrium (LD) structure. (A) A diagram showing the exonic structure of DISC1 gene (black). The single nucleotide polymorphisms (SNPs) used in this study are shown in relation to the exons. (B)The linkage disequilibrium (LD) structure of the DISC1 region in the total autism samples according to Haploview (solid spine of LD, D'> 0.7). Markers with LD (D' < 1 and LOD > 2) are shown in red through pink (color intensity decreases with decreasing D' value). Regions of low LD (D' < 1 and LOD < 2) are shown in white. Two blocks were generated by Haploview.

Mentions: Genomic DNA was extracted from the blood using a Qiagen QIAamp DNA Mini Kit. We selected seven single nucleotide polymorphisms (SNPs) in the DISC1 gene according to the dbSNP http://www.ncbi.nlm.nih.gov/SNP/ and the HapMap phase Ⅱ Chinese Han in Beijing (CHB) genotype dataset http://hapmap.ncbi.nlm.nih.gov/, including rs4366301, rs11585959, rs1322784, rs6668845, rs10864698, rs872624 in introns and rs821616 in exon (Figure 1). SNPs with minor allele frequency (MAF) >0.05 were selected and pair-wise tagging in the Tagger module implemented in Haploview v4.1 program was used to select SNPs that could capture >80% of the markers with r2>0.8. Meanwhile, the physical position of SNPs and the previous positive results were considered too.


Evidence for association between Disrupted-in-Schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based association study.

Zheng F, Wang L, Jia M, Yue W, Ruan Y, Lu T, Liu J, Li J, Zhang D - Behav Brain Funct (2011)

DISC1 gene locus and linkage disequilibrium (LD) structure. (A) A diagram showing the exonic structure of DISC1 gene (black). The single nucleotide polymorphisms (SNPs) used in this study are shown in relation to the exons. (B)The linkage disequilibrium (LD) structure of the DISC1 region in the total autism samples according to Haploview (solid spine of LD, D'> 0.7). Markers with LD (D' < 1 and LOD > 2) are shown in red through pink (color intensity decreases with decreasing D' value). Regions of low LD (D' < 1 and LOD < 2) are shown in white. Two blocks were generated by Haploview.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3113723&req=5

Figure 1: DISC1 gene locus and linkage disequilibrium (LD) structure. (A) A diagram showing the exonic structure of DISC1 gene (black). The single nucleotide polymorphisms (SNPs) used in this study are shown in relation to the exons. (B)The linkage disequilibrium (LD) structure of the DISC1 region in the total autism samples according to Haploview (solid spine of LD, D'> 0.7). Markers with LD (D' < 1 and LOD > 2) are shown in red through pink (color intensity decreases with decreasing D' value). Regions of low LD (D' < 1 and LOD < 2) are shown in white. Two blocks were generated by Haploview.
Mentions: Genomic DNA was extracted from the blood using a Qiagen QIAamp DNA Mini Kit. We selected seven single nucleotide polymorphisms (SNPs) in the DISC1 gene according to the dbSNP http://www.ncbi.nlm.nih.gov/SNP/ and the HapMap phase Ⅱ Chinese Han in Beijing (CHB) genotype dataset http://hapmap.ncbi.nlm.nih.gov/, including rs4366301, rs11585959, rs1322784, rs6668845, rs10864698, rs872624 in introns and rs821616 in exon (Figure 1). SNPs with minor allele frequency (MAF) >0.05 were selected and pair-wise tagging in the Tagger module implemented in Haploview v4.1 program was used to select SNPs that could capture >80% of the markers with r2>0.8. Meanwhile, the physical position of SNPs and the previous positive results were considered too.

Bottom Line: However, the results were not replicated in Korean population.After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant.These results were still significant after using the permutation method to obtain empirical p values.

View Article: PubMed Central - HTML - PubMed

Affiliation: Key Laboratory for Mental Health, Ministry of Health, Beijing, PR China.

ABSTRACT

Background: Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism.

Methods: We genotyped seven tag single nucleotide polymorphisms (SNPs) in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software.

Results: We found three SNPs showed significant associations with autism (rs4366301: G>C, Z=2.872, p=0.004; rs11585959: T>C, Z=2.199, p=0.028; rs6668845: A>G, Z=2.326, p=0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values.

Conclusions: Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism.

Show MeSH
Related in: MedlinePlus