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PMID |
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TITLE |
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Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. |
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ABSTRACT |
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BACKGROUND |
NlmCategory: BACKGROUND |
Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. |
METHODS |
NlmCategory: METHODS |
Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease. |
RESULTS |
NlmCategory: RESULTS |
We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10(-11)). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. |
CONCLUSIONS |
NlmCategory: CONCLUSIONS |
We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder. |
Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
received |
2015/12/01 |
revised |
2016/03/26 |
accepted |
2016/05/05 |
entrez |
2016/08/14 06:00 |
pubmed |
2016/08/16 06:00 |
medline |
2016/08/16 06:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Power RA |
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Power |
Robert A |
RA |
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Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London. |
Tansey KE |
|
Tansey |
Katherine E |
KE |
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MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom. |
Buttenschøn HN |
|
Buttenschøn |
Henriette Nørmølle |
HN |
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Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. |
Cohen-Woods S |
|
Cohen-Woods |
Sarah |
S |
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Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia. |
Bigdeli T |
|
Bigdeli |
Tim |
T |
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Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia. |
Hall LS |
|
Hall |
Lynsey S |
LS |
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Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom. |
Kutalik Z |
|
Kutalik |
Zoltán |
Z |
|
Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. |
Lee SH |
|
Lee |
S Hong |
SH |
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Queensland Brain Institute, The University of Queensland, Brisbane, Queensland; School of Environmental and Rural Science, University of New England, Armidale, New South Wales, Australia. |
Ripke S |
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Ripke |
Stephan |
S |
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Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Psychiatry and Psychotherapy, Charité, Campus Mitte, Berlin, Germany. |
Steinberg S |
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Steinberg |
Stacy |
S |
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deCODE Genetics, Reykjavik, Iceland. |
Teumer A |
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Teumer |
Alexander |
A |
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Institute for Community Medicine, 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. |
Wray NR |
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Wray |
Naomi R |
NR |
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Queensland Brain Institute, The University of Queensland, Brisbane, Queensland. |
Arolt V |
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Arolt |
Volker |
V |
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Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany. |
Baune BT |
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Baune |
Bernard T |
BT |
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Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia. |
Boomsma DI |
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Boomsma |
Dorret I |
DI |
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Department of Biological Psychology, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands. |
Børglum AD |
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Børglum |
Anders D |
AD |
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Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark; Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. |
Byrne EM |
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Byrne |
Enda M |
EM |
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Queensland Brain Institute, The University of Queensland, Brisbane, Queensland. |
Castelao E |
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Castelao |
Enrique |
E |
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Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland. |
Craddock N |
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Craddock |
Nick |
N |
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MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom. |
Craig IW |
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Craig |
Ian W |
IW |
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Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London. |
Dannlowski U |
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Dannlowski |
Udo |
U |
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Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany; Department of Psychiatry, University of Marburg, Marburg, Germany. |
Deary IJ |
|
Deary |
Ian J |
IJ |
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Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom. |
Degenhardt F |
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Degenhardt |
Franziska |
F |
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Institute of Human Genetics; Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. |
Forstner AJ |
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Forstner |
Andreas J |
AJ |
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Institute of Human Genetics; Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. |
Gordon SD |
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Gordon |
Scott D |
SD |
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QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
Grabe HJ |
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Grabe |
Hans J |
HJ |
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Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. |
Grove J |
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Grove |
Jakob |
J |
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Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark; Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. |
Hamilton SP |
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Hamilton |
Steven P |
SP |
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Department of Psychiatry, Kaiser Permanente San Francisco Medical Center, San Francisco, California. |
Hayward C |
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Hayward |
Caroline |
C |
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Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom. |
Heath AC |
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Heath |
Andrew C |
AC |
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Department of Psychiatry, Washington University St. Louis, St. Louis, Missouri. |
Hocking LJ |
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Hocking |
Lynne J |
LJ |
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Division of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom. |
Homuth G |
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Homuth |
Georg |
G |
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Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald. |
Hottenga JJ |
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Hottenga |
Jouke J |
JJ |
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Department of Biological Psychology, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands. |
Kloiber S |
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Kloiber |
Stefan |
S |
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Max Planck Institute of Psychiatry, Munich, Germany. |
Krogh J |
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Krogh |
Jesper |
J |
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Mental Health Center Copenhagen, Mental Health Services in Capital Region, University of Copenhagen, Copenhagen, Denmark. |
Landén M |
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Landén |
Mikael |
M |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden. |
Lang M |
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Lang |
Maren |
M |
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Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. |
Levinson DF |
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Levinson |
Douglas F |
DF |
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Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California. |
Lichtenstein P |
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Lichtenstein |
Paul |
P |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
Lucae S |
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Lucae |
Susanne |
S |
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Max Planck Institute of Psychiatry, Munich, Germany. |
MacIntyre DJ |
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MacIntyre |
Donald J |
DJ |
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Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom. |
Madden P |
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Madden |
Pamela |
P |
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Department of Psychiatry, Washington University St. Louis, St. Louis, Missouri. |
Magnusson PK |
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Magnusson |
Patrik K E |
PK |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
Martin NG |
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Martin |
Nicholas G |
NG |
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QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
McIntosh AM |
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McIntosh |
Andrew M |
AM |
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Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, United Kingdom. |
Middeldorp CM |
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Middeldorp |
Christel M |
CM |
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Department of Biological Psychology, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands. |
Milaneschi Y |
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Milaneschi |
Yuri |
Y |
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Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. |
Montgomery GW |
|
Montgomery |
Grant W |
GW |
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QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
Mors O |
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Mors |
Ole |
O |
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Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark; Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark. |
Müller-Myhsok B |
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Müller-Myhsok |
Bertram |
B |
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Max Planck Institute of Psychiatry, Munich, Germany; Munich Cluster for Systems Neurology, Munich, Germany; Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom. |
Nyholt DR |
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Nyholt |
Dale R |
DR |
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Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. |
Oskarsson H |
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Oskarsson |
Hogni |
H |
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Therapeia, Reykjavik, Iceland. |
Owen MJ |
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Owen |
Michael J |
MJ |
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MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom. |
Padmanabhan S |
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Padmanabhan |
Sandosh |
S |
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Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom. |
Penninx BW |
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Penninx |
Brenda W J H |
BW |
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Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. |
Pergadia ML |
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Pergadia |
Michele L |
ML |
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Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida. |
Porteous DJ |
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Porteous |
David J |
DJ |
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Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom. |
Potash JB |
|
Potash |
James B |
JB |
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Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa. |
Preisig M |
|
Preisig |
Martin |
M |
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Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland. |
Rivera M |
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Rivera |
Margarita |
M |
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Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London; CIBERSAM-Universidad de Granada e Instituto de Investigación Biosanitaria ibs, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. |
Shi J |
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Shi |
Jianxin |
J |
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Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. |
Shyn SI |
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Shyn |
Stanley I |
SI |
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Department of Psychiatry, Group Health, Seattle, Washington. |
Sigurdsson E |
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Sigurdsson |
Engilbert |
E |
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University of Iceland; Department of Psychiatry, Landspitali University Hospital, Reykjavik, Iceland. |
Smit JH |
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Smit |
Johannes H |
JH |
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Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. |
Smith BH |
|
Smith |
Blair H |
BH |
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Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom. |
Stefansson H |
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Stefansson |
Hreinn |
H |
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deCODE Genetics, Reykjavik, Iceland. |
Stefansson K |
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Stefansson |
Kari |
K |
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deCODE Genetics, Reykjavik, Iceland. |
Strohmaier J |
|
Strohmaier |
Jana |
J |
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Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. |
Sullivan PF |
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Sullivan |
Patrick F |
PF |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. |
Thomson P |
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Thomson |
Pippa |
P |
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Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, United Kingdom; Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom. |
Thorgeirsson TE |
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Thorgeirsson |
Thorgeir E |
TE |
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deCODE Genetics, Reykjavik, Iceland. |
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. |
Weissman MM |
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Weissman |
Myrna M |
MM |
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College of Physicians and Surgeons and the Mailman School of Public Health, Columbia University and New York State Psychiatric Institute, New York, New York. |
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CONVERGE Consortium, CARDIoGRAM Consortium, GERAD1 Consortium |
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Breen G |
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Breen |
Gerome |
G |
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Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London. |
Lewis CM |
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Lewis |
Cathryn M |
CM |
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Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London. Electronic address: cathryn.lewis@kcl.ac.uk. |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: |
ISSUE: |
TITLE: Biological psychiatry |
ISOABBREVIATION: Biol. Psychiatry |
YEAR: 2016 |
MONTH: May |
DAY: 24 |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 1873-2402 |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: Biol Psychiatry |
COUNTRY: United States |
ISSNLINKING: 0006-3223 |
NLMUNIQUEID: 0213264 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
JOURNAL ARTICLE |
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COMMENTS AND CORRECTIONS |
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GRANTS |
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GENERAL NOTE |
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KEYWORDS |
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KEYWORD |
Age at onset |
GWAS |
Heterogeneity |
Major depressive disorder |
Polygenic scoring |
Stratification |
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MESH HEADINGS |
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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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