Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
32231276
TITLE
Minimal phenotyping yields genome-wide association signals of low specificity for major depression.
ABSTRACT
Minimal phenotyping refers to the reliance on the use of a small number of self-reported items for disease case identification, increasingly used in genome-wide association studies (GWAS). Here we report differences in genetic architecture between depression defined by minimal phenotyping and strictly defined major depressive disorder (MDD): the former has a lower genotype-derived heritability that cannot be explained by inclusion of milder cases and a higher proportion of the genome contributing to this shared genetic liability with other conditions than for strictly defined MDD. GWAS based on minimal phenotyping definitions preferentially identifies loci that are not specific to MDD, and, although it generates highly predictive polygenic risk scores, the predictive power can be explained entirely by large sample sizes rather than by specificity for MDD. Our results show that reliance on results from minimal phenotyping may bias views of the genetic architecture of MDD and impede the ability to identify pathways specific to MDD.
DATE PUBLISHED
2020 04
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2018/11/02
accepted 2020/02/19
pubmed 2020/04/02 06:00
medline 2020/06/27 06:00
entrez 2020/04/02 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Cai N Cai Na N Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany. na.cai@helmholtz-muenchen.de.
Revez JA Revez Joana A JA Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Adams MJ Adams Mark J MJ Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Andlauer TFM Andlauer Till F M TFM Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
Breen G Breen Gerome G Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK.
Byrne EM Byrne Enda M EM Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Clarke TK Clarke Toni-Kim TK Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Forstner AJ Forstner Andreas J AJ Centre for Human Genetics, University of Marburg, Marburg, Germany.
Grabe HJ Grabe Hans J HJ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Hamilton SP Hamilton Steven P SP Department of Psychiatry, Kaiser Permanente Northern California, San Francisco, CA, USA.
Levinson DF Levinson Douglas F DF Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA.
Lewis CM Lewis Cathryn M CM Department of Medical & Molecular Genetics, King's College London, London, UK.
Lewis G Lewis Glyn G Division of Psychiatry, University College London, London, UK.
Martin NG Martin Nicholas G NG Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Milaneschi Y Milaneschi Yuri Y Department of Psychiatry, Amsterdam UMC, Vrije Universiteit and GGZinGeest, Amsterdam, the Netherlands.
Mors O Mors Ole O iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Müller-Myhsok B Müller-Myhsok Bertram B Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Penninx BWJH Penninx Brenda W J H BWJH Department of Psychiatry, Amsterdam UMC, Vrije Universiteit and GGZinGeest, Amsterdam, the Netherlands.
Perlis RH Perlis Roy H RH Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Pistis G Pistis Giorgio G Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Potash JB Potash James B JB Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Preisig M Preisig Martin M Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Shi J Shi Jianxin J Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Smoller JW Smoller Jordan W JW Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
Streit F Streit Fabien F Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Tiemeier H Tiemeier Henning H Department of Social and Behavioral Science, Harvard TH Chan School of Public Health, Boston, MA, USA.
Uher R Uher Rudolf R Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
Van der Auwera S Van der Auwera Sandra S Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Viktorin A Viktorin Alexander A Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Weissman MM Weissman Myrna M MM Division of Translational Epidemiology, New York State Psychiatric Institute, New York, NY, USA.
MDD Working Group of the Psychiatric Genomics Consortium
Kendler KS Kendler Kenneth S KS Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
Flint J Flint Jonathan J Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
INVESTIGATORS
JOURNAL
VOLUME: 52
ISSUE: 4
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2020
MONTH: 04
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
Department of Health United Kingdom
U01 MH109528 NIMH NIH HHS United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Bipolar Disorder genetics
Depressive Disorder, Major genetics
Female genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study methods
Genotype methods
Humans methods
Male methods
Middle Aged methods
Multifactorial Inheritance genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
Risk Factors genetics
Sensitivity and Specificity genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's