Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium

doi:10.1038/s42003-018-0155-y

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium

Molecular Biosciences

King's College London
Universidade Federal de São Paulo
Pax Instituto de Psiquiatria
University of Queensland
Broad Institute
Charité – Universitätsmedizin Berlin
Massachusetts General Hospital
Aarhus University
Karolinska Institutet
University of Würzburg
Lundbeck Foundation Initiative for Integrative Psychiatric Research
University of Amsterdam
University of Edinburgh
University of Adelaide
Max Planck Institute of Psychiatry
Munich Cluster for Systems Neurology (SyNergy)
Virginia Commonwealth University
Statens Serum Institut
VU University Medical Center
Virginia Institute for Psychiatric and Behavioral Genetics
Emory University School of Medicine
Wellcome Trust Genome Campus
European Bioinformatics Institute
University Hospital Center
QIMR Berghofer Medical Research Institute
MRC Centre for Neuropsychiatric Genetics and Genomics
Duke University
Duke University School of Medicine
University of Bonn
Erasmus MC
Dokuz Eylül University
Cardiff University
University of British Columbia
Harvard School of Public Health
Massachusetts Institute of Technology
University of Basel
University of Basel
University of Heidelberg
Trinity College Dublin
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease
University Hospital of Copenhagen - Rigshospitalet
Mental Health Centre Sct. Hans
Sydney University Biological Informatics and Technology Centre (SUBIT)
University Medicine Greifswald
F. Hoffman-La Roche
University of Worcester
Kaiser Permanente Northern California
University of Southern California
Harvard Medical School
Brigham and Women's Hospital
Boston Children's Hospital
Wellcome Trust Centre for Human Genetics
Gentofte University Hospital
Lausanne University Hospital
Swiss Institute of Bioinformatics
NHS Greater Glasgow and Clyde
University of Oxford
Columbia University
Queensland University of Technology
Children’s Health Queensland
University of Tartu
Humus
Vrije Universiteit Amsterdam
Solid Biosciences
Washington University School of Medicine in St. Louis
Sport and Health University Research Institute (iMUDS)
University Medical Center Groningen
Ludwig-Maximilians-University
Southern California Permanente Medical Group
University of Iceland
James Cook University
University of Glasgow, G11 6NT
deCODE genetics
Cardiff University
University of Münster
Department of Psychiatry
Oslo University Hospital
University of Cambridge
Leiden University Medical Center
Pfizer Global Research and Development
University Hospital Basel
ICS-6/Structural Biochemistry
University of Trento
University Hospital Freiburg
MRC Human Genetics Unit
University of Toronto
Centre for Addiction and Mental Health
University College London
LLC
University of Tartu
Aarhus University Hospital
University of Liverpool
Copenhagen University Hospital
University of Iowa
University Medical Centre Göttingen
National Institute of Mental Health Intramural Research Program
Dalhousie University, Faculty of Medicine
New York State Psychiatric Institute
University of Copenhagen
Stanford University
University of North Carolina
Princess Margaret Hospital
University of Washington Medical Center
Icahn School of Medicine at Mount Sinai
Vanderbilt University Medical Center
University of Michigan School of Public Health
University of Michigan Medical School
University of Minnesota Twin Cities
HudsonAlpha Institute for Biotechnology
University of California
Joan and Sanford I. Weill Department of Medicine
University of Michigan Medical Center
University of Bergen
Norwegian University of Science and Technology (NTNU)
Trondheim University Hospital
Berkshire Healthcare NHS Foundation Trust
North East London NHS Foundation Trust
University of Pittsburgh
University of Gothenburg
Karolinska University Hospital
“Translationnal Psychiatry”
UMR-S955
Mondor University Hospitals
University Hospital Cologne
Neuroscience Research Australia
University of New South Wales
University Regional Hospital
Poznan University of Medical Sciences
Psychiatric Center Nordbaden
Kliniken des Bezirks Oberbayern
University Hospital Carl Gustav Carus
Intl. Agency for Research on Cancer
Barcelona Institute for Global Health
University of New South Wales Faculty of Medicine, School of Psychiatry
University of Tübingen
Scripps Translational Science Institute
Indiana University School of Medicine
University of Chicago
Rush University Medical Center
Howard University College of Medicine
University of California San Francisco
University of Pennsylvania
Ciccarone Center for the Prevention of Heart Disease
Translational Genomics Research Institute
University of Aberdeen School of Medicine, Medical Sciences and Nutrition
University of Birmingham
University of Dundee School of Medicine
Medical University of Sofia
McGill University
McGill University
McGill University
Alexandru Obregia Clinical Psychiatric Hospital
University Medical Centre Utrecht
McGill University
University of California
Umeå University
University of Antwerp
SUNY Downstate Medical Center
Mayo Clinic
Keck School of Medicine of USC
M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
Nofer Institute of Occupational Medicine
New South Wales Ministry of Health
Cardiff University School of Medicine
University of Toronto Faculty of Medicine
University of Agder
McGill University
Federal Institute for Drugs and Medical Devices (BfArM)
National Cancer Institute (NCI)

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

15 Citations (Scopus)

Abstract

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.

Original language	English
Article number	163
Journal	Communications Biology
Volume	1
Issue number	1
DOIs	https://doi.org/10.1038/s42003-018-0155-y
Publication status	Published - 1 Dec 2018

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10.1038/s42003-018-0155-y

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@article{ca308f2501e64c868e04819c8e98d392,

title = "Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder",

abstract = "Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n \textasciitilde{} 260) in which 30\% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.",

author = "\{Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium\} and \{de Jong\}, Simone and Diniz, \{Mateus Jose Abdalla\} and Andiara Saloma and Ary Gadelha and Santoro, \{Marcos L.\} and Ota, \{Vanessa K.\} and Cristiano Noto and Wray, \{Naomi R.\} and Stephan Ripke and Manuel Mattheisen and Maciej Trzaskowski and Byrne, \{Enda M.\} and Abdel Abdellaoui and Adams, \{Mark J.\} and Esben Agerbo and Air, \{Tracy M.\} and Andlauer, \{Till F.M.\} and Bacanu, \{Silviu Alin\} and Marie B{\ae}kvad-Hansen and Beekman, \{Aartjan T.F.\} and Bigdeli, \{Tim B.\} and Binder, \{Elisabeth B.\} and Blackwood, \{Douglas H.R.\} and Julien Bryois and Buttensch{\o}n, \{Henriette N.\} and Jonas Bybjerg-Grauholm and Na Cai and Enrique Castelao and Christensen, \{Jane Hvarregaard\} and Clarke, \{Toni Kim\} and Coleman, \{Jonathan R.I.\} and Luc{\'i}a Colodro-Conde and Baptiste Couvy-Duchesne and Nick Craddock and Crawford, \{Gregory E.\} and Gail Davies and Deary, \{Ian J.\} and Franziska Degenhardt and Derks, \{Eske M.\} and Nese Direk and Dolan, \{Conor V.\} and Dunn, \{Erin C.\} and Eley, \{Thalia C.\} and Valentina Escott-Price and Kiadeh, \{Farnush Farhadi Hassan\} and Finucane, \{Hilary K.\} and Forstner, \{Andreas J.\} and Josef Frank and Gaspar, \{H{\'e}l{\'e}na A.\} and Michael Gill and Goes, \{Fernando S.\} and Gordon, \{Scott D.\} and Jakob Grove and Hansen, \{Christine S{\o}holm\} and Hansen, \{Thomas F.\} and Stefan Herms and Hickie, \{Ian B.\} and Per Hoffmann and Georg Homuth and Carsten Horn and Hottenga, \{Jouke Jan\} and Hougaard, \{David M.\} and Marcus Ising and Rick Jansen and Ian Jones and Jones, \{Lisa A.\} and Eric Jorgenson and Knowles, \{James A.\} and Kohane, \{Isaac S.\} and Julia Kraft and Kretzschmar, \{Warren W.\} and Jesper Krogh and Zolt{\'a}n Kutalik and Yihan Li and Lind, \{Penelope A.\} and MacIntyre, \{Donald J.\} and MacKinnon, \{Dean F.\} and Maier, \{Robert M.\} and Wolfgang Maier and Jonathan Marchini and Hamdi Mbarek and Patrick McGrath and Peter McGuffin and Medland, \{Sarah E.\} and Divya Mehta and Middeldorp, \{Christel M.\} and Evelin Mihailov and Yuri Milaneschi and Lili Milani and Mondimore, \{Francis M.\} and Montgomery, \{Grant W.\} and Sara Mostafavi and Niamh Mullins and Matthias Nauck and Bernard Ng and Nivard, \{Michel G.\} and Nyholt, \{Dale R.\} and Hogni Oskarsson and Owen, \{Michael J.\} and Derek Morris",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s42003-018-0155-y",

language = "English",

volume = "1",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

}

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder. / Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium.
In: Communications Biology, Vol. 1, No. 1, 163, 01.12.2018.

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

TY - JOUR

T1 - Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

AU - Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium

AU - de Jong, Simone

AU - Diniz, Mateus Jose Abdalla

AU - Saloma, Andiara

AU - Gadelha, Ary

AU - Santoro, Marcos L.

AU - Ota, Vanessa K.

AU - Noto, Cristiano

AU - Wray, Naomi R.

AU - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

AU - Adams, Mark J.

AU - Agerbo, Esben

AU - Air, Tracy M.

AU - Andlauer, Till F.M.

AU - Bacanu, Silviu Alin

AU - Bækvad-Hansen, Marie

AU - Beekman, Aartjan T.F.

AU - Bigdeli, Tim B.

AU - Binder, Elisabeth B.

AU - Blackwood, Douglas H.R.

AU - Bryois, Julien

AU - Buttenschøn, Henriette N.

AU - Bybjerg-Grauholm, Jonas

AU - Cai, Na

AU - Castelao, Enrique

AU - Christensen, Jane Hvarregaard

AU - Clarke, Toni Kim

AU - Coleman, Jonathan R.I.

AU - Colodro-Conde, Lucía

AU - Couvy-Duchesne, Baptiste

AU - Craddock, Nick

AU - Crawford, Gregory E.

AU - Davies, Gail

AU - Deary, Ian J.

AU - Degenhardt, Franziska

AU - Derks, Eske M.

AU - Direk, Nese

AU - Dolan, Conor V.

AU - Dunn, Erin C.

AU - Eley, Thalia C.

AU - Escott-Price, Valentina

AU - Kiadeh, Farnush Farhadi Hassan

AU - Finucane, Hilary K.

AU - Forstner, Andreas J.

AU - Frank, Josef

AU - Gaspar, Héléna A.

AU - Gill, Michael

AU - Goes, Fernando S.

AU - Gordon, Scott D.

AU - Grove, Jakob

AU - Hansen, Christine Søholm

AU - Hansen, Thomas F.

AU - Herms, Stefan

AU - Hickie, Ian B.

AU - Hoffmann, Per

AU - Homuth, Georg

AU - Horn, Carsten

AU - Hottenga, Jouke Jan

AU - Hougaard, David M.

AU - Ising, Marcus

AU - Jansen, Rick

AU - Jones, Ian

AU - Jones, Lisa A.

AU - Jorgenson, Eric

AU - Knowles, James A.

AU - Kohane, Isaac S.

AU - Kraft, Julia

AU - Kretzschmar, Warren W.

AU - Krogh, Jesper

AU - Kutalik, Zoltán

AU - Li, Yihan

AU - Lind, Penelope A.

AU - MacIntyre, Donald J.

AU - MacKinnon, Dean F.

AU - Maier, Robert M.

AU - Maier, Wolfgang

AU - Marchini, Jonathan

AU - Mbarek, Hamdi

AU - McGrath, Patrick

AU - McGuffin, Peter

AU - Medland, Sarah E.

AU - Mehta, Divya

AU - Middeldorp, Christel M.

AU - Mihailov, Evelin

AU - Milaneschi, Yuri

AU - Milani, Lili

AU - Mondimore, Francis M.

AU - Montgomery, Grant W.

AU - Mostafavi, Sara

AU - Mullins, Niamh

AU - Nauck, Matthias

AU - Ng, Bernard

AU - Nivard, Michel G.

AU - Nyholt, Dale R.

AU - Oskarsson, Hogni

AU - Owen, Michael J.

AU - Morris, Derek

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.

AB - Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.

UR - https://www.scopus.com/pages/publications/85061101811

U2 - 10.1038/s42003-018-0155-y

DO - 10.1038/s42003-018-0155-y

M3 - Article

SN - 2399-3642

VL - 1

JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 163

ER -

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Abstract

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