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A genome-wide association study in 574 schizophrenia trios using DNA pooling

Molecular Psychiatry volume 14, pages 796–803 (2009)Cite this article

Abstract

The cost of genome-wide association (GWA) studies can be prohibitively high when large samples are genotyped. We conducted a GWA study on schizophrenia (SZ) and to reduce the cost, we used DNA pooling. We used a parent–offspring trios design to avoid the potential problems of population stratification. We constructed pools from 605 unaffected controls, 574 SZ patients and a third pool from all the parents of the patients. We hybridized each pool eight times on Illumina HumanHap550 arrays. We estimated the allele frequencies of each pool from the averaged intensities of the arrays. The significance level of results in the trios sample was estimated on the basis of the allele frequencies in cases and non-transmitted pseudocontrols, taking into account the technical variability of the data. We selected the highest ranked SNPs for individual genotyping, after excluding poorly performing SNPs and those that showed a trend in the opposite direction in the control pool. We genotyped 63 SNPs in 574 trios and analysed the results with the transmission disequilibrium test. Forty of those were significant at P<0.05, with the best result at P=1.2 × 10−6 for rs11064768. This SNP is within the gene CCDC60, a coiled-coil domain gene. The third best SNP (P=0.00016) is rs893703, within RBP1, a candidate gene for schizophrenia.

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Acknowledgements

This work was funded by the International Centre for Genetic Engineering and Biotechnology, Trieste, grant to the Department of Medical Genetics, Sofia (CRP/BUL04-01) and a Schizophrenia programme grant from the MRC to the Department of Psychological Medicine, Cardiff University (ref G9309834). The recruitment of trios was funded by the Janssen Research Foundation, Beerse, Belgium.

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Authors and Affiliations

  1. Department of Psychological Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff, UK

    G Kirov, L Georgieva, V Moskvina, I Nikolov, M J Owen & M C O'Donovan

  2. Department of Medical Genetics, University Hospital ‘Maichin Dom’, Sofia, Bulgaria

    I Zaharieva & D Toncheva

  3. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany

    S Cichon & A Hillmer

Authors
  1. G Kirov
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  2. I Zaharieva
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  3. L Georgieva
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  4. V Moskvina
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  5. I Nikolov
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  6. S Cichon
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  7. A Hillmer
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  8. D Toncheva
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  9. M J Owen
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  10. M C O'Donovan
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Correspondence to G Kirov.

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Kirov, G., Zaharieva, I., Georgieva, L. et al. A genome-wide association study in 574 schizophrenia trios using DNA pooling. Mol Psychiatry 14, 796–803 (2009). https://doi.org/10.1038/mp.2008.33

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