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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
  • 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
  • The 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 Centre Amsterdam
  • Emory University
  • Wellcome Trust Sanger Institute
  • European Molecular Biology Laboratory
  • University of Lausanne
  • Queensland Institute of Medical Research
  • Cardiff University
  • Duke University
  • University of Bonn
  • Erasmus University Rotterdam
  • Dokuz Eylul University
  • University of British Columbia
  • Harvard University
  • Massachusetts Institute of Technology
  • University of Basel
  • Heidelberg University 
  • Trinity College Dublin
  • Johns Hopkins University
  • University of Copenhagen
  • Mental Health Services Capital Region of Denmark
  • The University of Sydney
  • University of Greifswald
  • F. Hoffmann-La Roche AG
  • University of Worcester
  • Kaiser Permanente
  • University of Southern California
  • Brigham and Women’s Hospital
  • Boston Children's Hospital
  • University of Oxford
  • Swiss Institute of Bioinformatics
  • NHS Greater Glasgow and Clyde
  • Columbia University
  • Queensland University of Technology
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  • Vrije Universiteit Amsterdam
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  • Washington University St. Louis
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  • University of Groningen
  • Ludwig Maximilian University of Munich
  • University of Iceland
  • James Cook University Queensland
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  • deCODE genetics
  • University of Münster
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  • Pfizer
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  • HudsonAlpha Institute for Biotechnology
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  • Cornell University
  • University of Bergen
  • Norwegian University of Science and Technology
  • Berkshire Healthcare NHS Foundation Trust
  • North East London NHS Foundation Trust
  • University of Pittsburgh
  • University of Gothenburg
  • Psychiatrie Translationnelle
  • UMR-S955
  • Assistance publique – Hôpitaux de Paris
  • University of Cologne
  • Neuroscience Research Australia
  • University of New South Wales
  • University Regional Hospital
  • University of Medical Sciences Poznan
  • Psychiatric Center Nordbaden
  • Kliniken des Bezirks Oberbayern
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  • Maria Sklodowska-Curie Institute of Oncology
  • Nofer Institute of Occupational Medicine
  • New South Wales Ministry of Health
  • University of Agder
  • Federal Institute for Drugs and Medical Devices (BfArM)

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article number163
JournalCommunications Biology
Volume1
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018
Externally publishedYes

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