Manuel Mattheisen

Quantifying between-cohort and between-sex genetic heterogeneity in major depressive disorder

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Maciej Trzaskowski, Univ Queensland, University of Queensland, Inst Mol Biosci
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  • Divya Mehta, Queensland Univ Technol, Queensland University of Technology (QUT), Sch Psychol & Counselling
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  • Wouter J. Peyrot, GGZ Geest
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  • David Hawkes, Univ Queensland, University of Queensland, AGRF
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  • Daniel Davies, Univ Cambridge, University of Cambridge, Dept Psychiat, Behav & Clin Biosci Inst & Dev Psychiat
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  • David M. Howard, Univ Edinburgh, Royal Infirmary of Edinburgh, University of Edinburgh, Royal Edinburgh Hosp, Div Psychiat
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  • Kathryn E. Kemper, Univ Queensland, University of Queensland, Inst Mol Biosci
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  • Julia Sidorenko, Univ Queensland, University of Queensland, Inst Mol Biosci
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  • Robert Maier, Harvard Med Sch, Harvard University, Harvard Medical School, Dept Psychiat
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  • Stephan Ripke, Univ Med Berlin, Humboldt University of Berlin, Free University of Berlin, Charite Medical University of Berlin, Charite Mitte Campus, Dept Psychiat & Psychotherapy, Campus Charite Mitte
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  • Manuel Mattheisen
  • Bernhard T. Baune, Univ Melbourne, University of Melbourne, Melbourne Med Sch, Dept Psychiat
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  • Hans J. Grabe, Univ Med Greifswald, Greifswald Medical School, Dept Psychiat & Psychotherapy
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  • Andrew C. Heath, Washington Univ, Washington University (WUSTL), Sch Med, Dept Psychiat
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  • Lisa Jones, Univ Worcester, University of Worcester, Inst Hlth & Soc
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  • Ian Jones, Cardiff Univ, Cardiff University, MRC Ctr Neuropsychiat Genet & Gen, Sch Med, Dept Psychol Med & Neurol
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  • Pamela A. F. Madden, Washington Univ, Washington University (WUSTL), Sch Med, Dept Psychiat
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  • Andrew M. McIntosh, Univ Edinburgh, University of Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol
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  • Gerome Breen, Kings Coll London, University of London, King's College London, NIHR BRC Mental Hlth
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  • Cathryn M. Lewis, Kings Coll London, University of London, King's College London, Dept Med & Mol Genet
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  • Anders D. Borglum, Aarhus Univ, Aarhus University, Ctr Integrat Sequencing, iSEQ
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  • Patrick F. Sullivan, Univ N Carolina, University of North Carolina, University of North Carolina Chapel Hill, Dept Psychiat
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  • Nicholas G. Martin, QIMR Berghofer Med Res Inst, QIMR Berghofer Medical Research Institute, Dept Genet & Computat Biol
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  • Kenneth S. Kendler, Virginia Commonwealth Univ, Virginia Commonwealth University, Dept Psychiat
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  • Douglas F. Levinson, Stanford Univ, Stanford University, Psychiat & Behav Sci
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  • Naomi R. Wray, Univ Queensland, University of Queensland, Queensland Brain Inst
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  • Major Depress Disorder Working G

Major depressive disorder (MDD) is clinically heterogeneous with prevalence rates twice as high in women as in men. There are many possible sources of heterogeneity in MDD most of which are not measured in a sufficiently comparable way across study samples. Here, we assess genetic heterogeneity based on two fundamental measures, between-cohort and between-sex heterogeneity. First, we used genome-wide association study (GWAS) summary statistics to investigate between-cohort genetic heterogeneity using the 29 research cohorts of the Psychiatric Genomics Consortium (PGC; N cases = 16,823, N controls = 25,632) and found that some of the cohort heterogeneity can be attributed to ascertainment differences (such as recruitment of cases from hospital vs. community sources). Second, we evaluated between-sex genetic heterogeneity using GWAS summary statistics from the PGC, Kaiser Permanente GERA, UK Biobank, and the Danish iPSYCH studies but did not find convincing evidence for genetic differences between the sexes. We conclude that there is no evidence that the heterogeneity between MDD data sets and between sexes reflects genetic heterogeneity. Larger sample sizes with detailed phenotypic records and genomic data remain the key to overcome heterogeneity inherent in assessment of MDD.

Original languageEnglish
JournalAmerican Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Volume180
Issue6
Pages (from-to)439-447
Number of pages9
ISSN1552-4841
DOIs
Publication statusPublished - Sep 2019

    Research areas

  • depression, genetic heterogeneity, LD score regression, MDD, sex differences, GENOME-WIDE ASSOCIATION, SCORE REGRESSION, CHILDHOOD TRAUMA, EPIDEMIOLOGY, WOMEN, HERITABILITY, NETHERLANDS, DISEASE, HEALTH, NESDA

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