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Replication of association of 3p21.1 with susceptibility to bipolar disorder but not major depression

Nature Genetics volume 43, pages 3–5 (2011)Cite this article

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To the Editor:

McMahon and colleagues1 recently reported a genome-wide significant association of rs2251219 on chromosome 3p21.1 with mood disorders in a combined sample of individuals with bipolar affective disorder (BP, also known as 'manic depression') and individuals with major depressive disorder (MDD). They meta-analyzed published data from four genome-wide association studies (GWAS) of BP2,3,4,5 and three published GWAS of MDD6,7, plus an unpublished German BP sample. Their analysis supports the suggestive association with bipolar disorder in this region previously reported by Scott et al.3 in a GWAS meta-analysis of three of the same BP samples (National Institute of Mental Health-BP4, Wellcome Trust Case Control Consortium2 and the GlaxoSmithKline-BP samples3), but we report here alternative analyses and new data inconsistent with an association in this region with MDD. Thus, rs2251219 appears to be a susceptibility locus for BP alone, and the data do not support a general association of this SNP with mood disorders.

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Acknowledgements

We thank the participants in the studies whose data we analyzed. We acknowledge funding from NARSAD, the UK Medical Research Council and Wellcome Trust and UK National Institute for Health Research, the US National Institutes of Health and National Institute of Mental Health and The Netherlands Scientific Organization.

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Authors and Affiliations

  1. Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK

    Gerome Breen, Cathryn M Lewis, Evangelos Vassos, Inti Pedroso, David Collier & Peter McGuffin

  2. National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust and Institute of Psychiatry, King's College London, London, UK

    Gerome Breen, Inti Pedroso & Peter McGuffin

  3. Medical and Molecular Genetics, King's College London, London, UK

    Cathryn M Lewis

  4. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA

    Michele L Pergadia

  5. Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburg, UK

    Douglas H R Blackwood

  6. Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    Dorret I Boomsma

  7. Department of Psychiatry, Vrije University Amsterdam, Amsterdam, The Netherlands

    Brenda Penninx

  8. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA

    Patrick F Sullivan

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  1. Gerome Breen
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Contributions

G.B., C.M.L., I.P. and E.V. performed the data analysis. G.B., D.C. and P.M. wrote the manuscript. M.L.P., D.H.R.B., B.P., D.I.B. and P.F.S. provided additional replication data and comments.

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Correspondence to Gerome Breen.

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Breen, G., Lewis, C., Vassos, E. et al. Replication of association of 3p21.1 with susceptibility to bipolar disorder but not major depression. Nat Genet 43, 3–5 (2011). https://doi.org/10.1038/ng0111-3

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