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PMID |
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TITLE |
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Minimal phenotyping yields genome-wide association signals of low specificity for major depression. |
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ABSTRACT |
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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. |
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DATE PUBLISHED |
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HISTORY |
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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 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Cai N |
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Cai |
Na |
N |
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Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany. na.cai@helmholtz-muenchen.de. |
Revez JA |
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Revez |
Joana A |
JA |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. |
Adams MJ |
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Adams |
Mark J |
MJ |
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Division of Psychiatry, University of Edinburgh, Edinburgh, UK. |
Andlauer TFM |
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Andlauer |
Till F M |
TFM |
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Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany. |
Breen G |
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Breen |
Gerome |
G |
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Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK. |
Byrne EM |
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Byrne |
Enda M |
EM |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. |
Clarke TK |
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Clarke |
Toni-Kim |
TK |
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Division of Psychiatry, University of Edinburgh, Edinburgh, UK. |
Forstner AJ |
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Forstner |
Andreas J |
AJ |
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Centre for Human Genetics, University of Marburg, Marburg, Germany. |
Grabe HJ |
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Grabe |
Hans J |
HJ |
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Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. |
Hamilton SP |
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Hamilton |
Steven P |
SP |
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Department of Psychiatry, Kaiser Permanente Northern California, San Francisco, CA, USA. |
Levinson DF |
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Levinson |
Douglas F |
DF |
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Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA. |
Lewis CM |
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Lewis |
Cathryn M |
CM |
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Department of Medical & Molecular Genetics, King's College London, London, UK. |
Lewis G |
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Lewis |
Glyn |
G |
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Division of Psychiatry, University College London, London, UK. |
Martin NG |
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Martin |
Nicholas G |
NG |
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Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
Milaneschi Y |
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Milaneschi |
Yuri |
Y |
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Department of Psychiatry, Amsterdam UMC, Vrije Universiteit and GGZinGeest, Amsterdam, the Netherlands. |
Mors O |
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Mors |
Ole |
O |
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iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark. |
Müller-Myhsok B |
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Müller-Myhsok |
Bertram |
B |
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Institute of Translational Medicine, University of Liverpool, Liverpool, UK. |
Penninx BWJH |
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Penninx |
Brenda W J H |
BWJH |
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Department of Psychiatry, Amsterdam UMC, Vrije Universiteit and GGZinGeest, Amsterdam, the Netherlands. |
Perlis RH |
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Perlis |
Roy H |
RH |
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Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. |
Pistis G |
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Pistis |
Giorgio |
G |
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Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. |
Potash JB |
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Potash |
James B |
JB |
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Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. |
Preisig M |
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Preisig |
Martin |
M |
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Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. |
Shi J |
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Shi |
Jianxin |
J |
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Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. |
Smoller JW |
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Smoller |
Jordan W |
JW |
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Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA. |
Streit F |
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Streit |
Fabien |
F |
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Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany. |
Tiemeier H |
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Tiemeier |
Henning |
H |
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Department of Social and Behavioral Science, Harvard TH Chan School of Public Health, Boston, MA, USA. |
Uher R |
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Uher |
Rudolf |
R |
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Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. |
Van der Auwera S |
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Van der Auwera |
Sandra |
S |
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Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. |
Viktorin A |
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Viktorin |
Alexander |
A |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
Weissman MM |
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Weissman |
Myrna M |
MM |
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Division of Translational Epidemiology, New York State Psychiatric Institute, New York, NY, USA. |
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MDD Working Group of the Psychiatric Genomics Consortium |
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Kendler KS |
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Kendler |
Kenneth S |
KS |
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Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA. |
Flint J |
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Flint |
Jonathan |
J |
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Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA. |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: 52 |
ISSUE: 4 |
TITLE: Nature genetics |
ISOABBREVIATION: Nat. Genet. |
YEAR: 2020 |
MONTH: 04 |
DAY: |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 1546-1718 |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: Nat Genet |
COUNTRY: United States |
ISSNLINKING: 1061-4036 |
NLMUNIQUEID: 9216904 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Research Support, N.I.H., Extramural |
Research Support, Non-U.S. Gov't |
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COMMENTS AND CORRECTIONS |
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GRANTS |
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GRANTID |
AGENCY |
COUNTRY |
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Department of Health |
United Kingdom |
U01 MH109528 |
NIMH NIH HHS |
United States |
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Wellcome Trust |
United Kingdom |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Adult |
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Aged |
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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 |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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OTHER ID's |
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