Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1

Journal name:
Nature Genetics
Volume:
42,
Pages:
128–131
Year published:
DOI:
doi:10.1038/ng.523
Received
Accepted
Published online

The major mood disorders, which include bipolar disorder and major depressive disorder (MDD), are considered heritable traits, although previous genetic association studies have had limited success in robustly identifying risk loci. We performed a meta-analysis of five case-control cohorts for major mood disorder, including over 13,600 individuals genotyped on high-density SNP arrays. We identified SNPs at 3p21.1 associated with major mood disorders (rs2251219, P = 3.63 × 10−8; odds ratio = 0.87; 95% confidence interval, 0.83–0.92), with supportive evidence for association observed in two out of three independent replication cohorts. These results provide an example of a shared genetic susceptibility locus for bipolar disorder and MDD.

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Author information

Affiliations

  1. Unit on the Genetic Basis of Mood & Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.

    • Francis J McMahon,
    • Nirmala Akula,
    • Thomas G Schulze,
    • Sevilla D Detera-Wadleigh,
    • C J M Steele &
    • Jens R Wendland
  2. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany.

    • Thomas G Schulze,
    • René Breuer,
    • Jana Strohmaier &
    • Marcella Rietschel
  3. Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Verona, Italy.

    • Pierandrea Muglia &
    • Federica Tozzi
  4. Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

    • Pierandrea Muglia &
    • John B Vincent
  5. Department of Genomics, Life & Brain Center, Bonn, Germany.

    • Manuel Mattheisen,
    • Thomas W Mühleisen,
    • Markus M Nöthen &
    • Sven Cichon
  6. Institute of Human Genetics, University of Bonn, Bonn, Germany.

    • Manuel Mattheisen,
    • Thomas W Mühleisen,
    • Markus M Nöthen,
    • Sven Cichon &
    • Marcella Rietschel
  7. Institute of Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany.

    • Manuel Mattheisen
  8. Department of Psychiatry, University of Bonn, Bonn, Germany.

    • Wolfgang Maier
  9. Institute of Psychiatry, King's College London, London, UK.

    • Anne Farmer
  10. Max Planck Institute of Psychiatry, Munich, Germany.

    • Florian Holsboer
  11. University Hospital Center and University of Lausanne, Department of Psychiatry, Lausanne, Switzerland.

    • Martin Preisig
  12. A full membership list is provided in the Supplementary Note.

    • the Bipolar Disorder Genome Study (BiGS) Consortium

Consortia

  1. the Bipolar Disorder Genome Study (BiGS) Consortium

    • Nirmala Akula,
    • Thomas G Schulze,
    • Pierandrea Muglia,
    • Federica Tozzi,
    • Sevilla D Detera-Wadleigh,
    • C J M Steele,
    • René Breuer,
    • Jana Strohmaier,
    • Jens R Wendland,
    • Manuel Mattheisen,
    • Thomas W Mühleisen,
    • Wolfgang Maier,
    • Markus M Nöthen,
    • Sven Cichon,
    • Anne Farmer,
    • John B Vincent,
    • Florian Holsboer,
    • Martin Preisig,
    • Marcella Rietschel &
    • Francis J McMahon

Contributions

F.J.M. designed the study, led the analysis and wrote the manuscript. N.A., T.G.S. and C.J.M.S. contributed to the data management and analysis. S.D.D.-W., T.G.S., P.M., W.M., F.H., M.R., J.I.N. and H.J.E. (the latter two are members of the BiGS Consortium) edited the manuscript. J.R.W. performed the gene expression experiments. P.M., F.T., R.B., J.S., M.M., T.W.M., W.M, M.M.N., S.C., A.F., J.B.V., F.H., M.P., M.R. and BiGS Consortium members collected samples and/or shared genetic association results. All authors reviewed the manuscript.

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Supplementary information

PDF files

  1. Supplementary Text and Figures (600K)

    Supplementary Figures 1–2, Supplementary Tables 2–5 and Supplementary Note

Excel files

  1. Supplementary Table 1 (29M)

    Complete results of meta-analysis for 317,889 SNPs in five study samples.

Additional data