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    The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls.

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    Author
    Coleman, JRI; Gaspar, HA; Bryois, J; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Breen, G
    Date
    2020-07-15
    Source Title
    Biological Psychiatry
    Publisher
    Elsevier BV
    University of Melbourne Author/s
    Baune, Bernhard
    Affiliation
    Psychiatry
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Coleman, J. R. I., Gaspar, H. A., Bryois, J., Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium & Breen, G. (2020). The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls.. Biol Psychiatry, 88 (2), pp.169-184. https://doi.org/10.1016/j.biopsych.2019.10.015.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/253998
    DOI
    10.1016/j.biopsych.2019.10.015
    Open Access URL
    http://eprints.gla.ac.uk/208027/7/208027.pdf
    Abstract
    BACKGROUND: Mood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction. METHODS: To clarify the shared molecular genetic basis of major depressive disorder and bipolar disorder and to highlight disorder-specific associations, we meta-analyzed data from the latest Psychiatric Genomics Consortium genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; nonoverlapping N = 609,424). RESULTS: Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More loci from the Psychiatric Genomics Consortium analysis of major depression than from that for bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single-episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment-the relationship is positive in bipolar disorder but negative in major depressive disorder. CONCLUSIONS: The mood disorders share several genetic associations, and genetic studies of major depressive disorder and bipolar disorder can be combined effectively to enable the discovery of variants not identified by studying either disorder alone. However, we demonstrate several differences between these disorders. Analyzing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.

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