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Published on: June 15, 2011
A genome-wide association study in 574 schizophrenia trios using DNA pooling
G Kirov1, I Zaharieva, L Georgieva
1Department of Psychological Medicine, Cardiff University, Henry Wellcome Building, Cardiff, UK. kirov@cardiff.ac.uk
Molecular Psychiatry
|March 12, 2008
Summary
DNA pooling in genome-wide association studies (GWAS) significantly reduced costs for schizophrenia research. This method identified potential genetic markers for schizophrenia, including SNPs within CCDC60 and RBP1 genes.
Area of Science:
- Genetics
- Psychiatric Genetics
- Genomic Association Studies
Background:
- Genome-wide association studies (GWAS) are crucial for identifying genetic variants associated with complex diseases like schizophrenia.
- High genotyping costs in large-scale GWAS can be a significant barrier to research.
- DNA pooling offers a cost-effective alternative for genotyping in large cohorts.
Purpose of the Study:
- To investigate the utility of DNA pooling in a cost-effective genome-wide association study for schizophrenia.
- To identify novel single nucleotide polymorphisms (SNPs) associated with schizophrenia susceptibility.
- To validate findings using a parent-offspring trios design to mitigate population stratification.
Main Methods:
- A parent-offspring trios design was employed, with DNA pooling for initial screening.
- Pools were created for 605 controls, 574 schizophrenia cases, and parents of cases.
- Hybridization was performed eight times on Illumina HumanHap550 arrays, with allele frequencies estimated from averaged intensities.
Main Results:
- After initial pooling and selection, 63 SNPs were genotyped individually in 574 trios.
- The transmission disequilibrium test (TDT) revealed 40 significant SNPs (P<0.05).
- The top SNP, rs11064768 within the CCDC60 gene, showed a highly significant association (P=1.2 x 10(-6)).
- SNP rs893703 within the RBP1 gene was the third best result (P=0.00016), implicating RBP1 as a candidate gene for schizophrenia.
Conclusions:
- DNA pooling is a viable and cost-effective strategy for conducting GWAS in schizophrenia.
- The study identified promising SNPs, including rs11064768 (CCDC60) and rs893703 (RBP1), as potential genetic contributors to schizophrenia.
- Further investigation of these identified genes may provide insights into the genetic architecture of schizophrenia.
Related Concept Videos
01:11Genome-wide Association Studies-GWAS
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
01:29Biological Causes of Schizophrenia
Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin studies.
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin studies.