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Genome-wide association study of recurrent major depressive disorder in two European case–control cohorts

Molecular Psychiatry volume 15, pages 589–601 (2010)Cite this article

Abstract

Major depressive disorder (MDD) is a highly prevalent disorder with substantial heritability. Heritability has been shown to be substantial and higher in the variant of MDD characterized by recurrent episodes of depression. Genetic studies have thus far failed to identify clear and consistent evidence of genetic risk factors for MDD. We conducted a genome-wide association study (GWAS) in two independent datasets. The first GWAS was performed on 1022 recurrent MDD patients and 1000 controls genotyped on the Illumina 550 platform. The second was conducted on 492 recurrent MDD patients and 1052 controls selected from a population-based collection, genotyped on the Affymetrix 5.0 platform. Neither GWAS identified any SNP that achieved GWAS significance. We obtained imputed genotypes at the Illumina loci for the individuals genotyped on the Affymetrix platform, and performed a meta-analysis of the two GWASs for this common set of approximately half a million SNPs. The meta-analysis did not yield genome-wide significant results either. The results from our study suggest that SNPs with substantial odds ratio are unlikely to exist for MDD, at least in our datasets and among the relatively common SNPs genotyped or tagged by the half-million-loci arrays. Meta-analysis of larger datasets is warranted to identify SNPs with smaller effects or with rarer allele frequencies that contribute to the risk of MDD.

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Acknowledgements

We acknowledge all the participants in the studies. We thank numerous people at GSK and Max-Planck Institute, BKH Augsburg and Klinikum Ingolstadt in Germany and the Staff and the Department of Psychiatry and Internal Medicine at the University of Lausanne who have contributed to this project. In particular, GSK thanks Paul M Matthews for his support to the project over the past year and to Shyama Brewster for initiating and coordinating the first phase of recruitment at the Germany Sites.

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Author notes

  1. A Antoniades

    Present address: 11Current address: University of Cyprus, Cyprus.,

  2. L T Middleton

    Present address: 12Current address: Division of Neurosciences and Mental Health, Imperial College, London, UK.,

  3. A D Roses

    Present address: 13Current address: Duke University, Durham, NC, USA.,

Authors and Affiliations

  1. Genetics Division, Drug Discovery, GlaxoSmithKline R&D, Verona, Italy

    P Muglia, F Tozzi, C Francks & A Antoniades

  2. Genetics Division, Drug Discovery, GlaxoSmithKline R&D, Harlow, Essex, UK

    N W Galwey & R Upmanyu

  3. Genetics Division, Drug Discovery, GlaxoSmithKline R&D, Research Triangle Park, NC, USA

    X Q Kong & A D Roses

  4. Molecular Psychiatry, Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline R&D, Verona, Italy

    E Domenici

  5. Genetics Division, Drug Discovery, GlaxoSmithKline R&D, Greenford, Middlesex, UK

    J Perry & L T Middleton

  6. Department of Psychiatry, University Hospital Center and University of Lausanne, Lausanne, Switzerland

    S Rothen & M Preisig

  7. Department of Psychiatry, University Hospital of Geneva, Geveva, Switzerland

    S Rothen & C L Vandeleur

  8. Genetics Division, Drug Discovery, GlaxoSmithKline R&D, Upper Merion, PA, USA

    V Mooser

  9. Department of Internal Medicine, University Hospital Center and University of Lausanne, Lausanne, Switzerland

    G Waeber & P Vollenweider

  10. Max-Planck Institute of Psychiatry, Munich, Germany

    S Lucae, B Müller-Myhsok & F Holsboer

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  1. P Muglia
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Correspondence to P Muglia.

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Muglia, P., Tozzi, F., Galwey, N. et al. Genome-wide association study of recurrent major depressive disorder in two European case–control cohorts. Mol Psychiatry 15, 589–601 (2010). https://doi.org/10.1038/mp.2008.131

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