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Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database

Nature Genetics volume 40, pages 827–834 (2008)Cite this article

Abstract

In an effort to pinpoint potential genetic risk factors for schizophrenia, research groups worldwide have published over 1,000 genetic association studies with largely inconsistent results. To facilitate the interpretation of these findings, we have created a regularly updated online database of all published genetic association studies for schizophrenia ('SzGene'). For all polymorphisms having genotype data available in at least four independent case-control samples, we systematically carried out random-effects meta-analyses using allelic contrasts. Across 118 meta-analyses, a total of 24 genetic variants in 16 different genes (APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53 and TPH1) showed nominally significant effects with average summary odds ratios of ∼1.23. Seven of these variants had not been previously meta-analyzed. According to recently proposed criteria for the assessment of cumulative evidence in genetic association studies, four of the significant results can be characterized as showing 'strong' epidemiological credibility. Our project represents the first comprehensive online resource for systematically synthesized and graded evidence of genetic association studies in schizophrenia. As such, it could serve as a model for field synopses of genetic associations in other common and genetically complex disorders.

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Acknowledgements

Funding for this study was provided by the National Alliance on Research in Schizophrenia and Depression (to L.B.). F.K.K. was supported by a PENED training grant co-financed by E.U. European Social Fund and the Greek Ministry of Development, General Secretariat for Research and Technology. We are grateful to the Schizophrenia Research Forum for hosting SzGene on their website. In particular, we would like to thank A. Bumstead, H. Heimer, C. Knep and P. Noyes for the online adaptation of SzGene and many helpful discussions. We would further like to thank the members of the Scientific Advisory Board (currently including W. Byerly, G.D. Smith, J. Kennedy, D.F. Levinson and M. Owen) for their repeated review of the database and their helpful comments and suggestions during the development of this project.

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Authors and Affiliations

  1. Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Charlestown, 02129, Massachusetts, USA

    Nicole C Allen, Sachin Bagade, Rudolph E Tanzi & Lars Bertram

  2. Institute for Behavioral Genetics, University of Colorado, Boulder, 80309, Colorado, USA

    Matthew B McQueen

  3. Department of Hygiene and Epidemiology, Clinical and Molecular Epidemiology Unit, University of Ioannina School of Medicine, Ioannina, 45110, Greece

    John P A Ioannidis & Fotini K Kavvoura

  4. Biomedical Research Institute, Foundation for Research and Technology Hellas, Ioannina, 45110, Greece

    John P A Ioannidis

  5. Department of Medicine, Tufts University School of Medicine, Boston, 02110, Massachusetts, USA

    John P A Ioannidis

  6. National Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, 30341, Georgia, USA

    Muin J Khoury

Authors
  1. Nicole C Allen
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  4. John P A Ioannidis
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  8. Lars Bertram
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Contributions

This study was designed by L.B. (principal investigator). Literature searches, data entry and online curation of data was done by N.C.A. and S.B., with help from L.B. Analysis scripts were developed and written by M.B.M. and F.K.K., and analyses were done by N.C.A., F.K.K., J.P.A.I. and L.B. The manuscript was written by N.C.A. and L.B., with contributions from J.P.A.I, F.K.K., M.J.K. and R.E.T.

Corresponding author

Correspondence to Lars Bertram.

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Allen, N., Bagade, S., McQueen, M. et al. Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat Genet 40, 827–834 (2008). https://doi.org/10.1038/ng.171

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