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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
  • Institute of Psychiatry
  • Department of Psychiatry
  • Universidade Federal de São Paulo
  • Pax Instituto de Psiquiatria
  • Department of Morphology and Genetics
  • University of Queensland
  • Broad Institute
  • Department of Psychiatry and Psychotherapy
  • Charité – Universitätsmedizin Berlin
  • Analytic and Translational Genetics Unit
  • Massachusetts General Hospital
  • iSEQ
  • Aarhus University
  • Department of Biomedicine
  • Centre for Psychiatry Research
  • Karolinska Institutet
  • Department of Psychiatry
  • University of Würzburg
  • iPSYCH
  • The Lundbeck Foundation Initiative for Integrative Psychiatric Research
  • University of Amsterdam
  • Division of Psychiatry
  • University of Edinburgh
  • Centre for Integrated Register-based Research
  • Discipline of Psychiatry
  • Adelaide University
  • Department of Translational Research in Psychiatry
  • Max Planck Institute of Psychiatry
  • Munich Cluster for Systems Neurology (SyNergy)
  • Virginia Commonwealth University
  • Center for Neonatal Screening
  • Statens Serum Institut
  • Department of Psychiatry
  • VU University Medical Center
  • Emory University
  • Department of Medical Epidemiology and Biostatistics
  • Translational Neuropsychiatry Unit
  • Wellcome Trust Sanger Institute
  • Statistical Genomics and Systems Genetics
  • European Molecular Biology Laboratory
  • Department of Psychiatry
  • University of Lausanne
  • Genetics and Computational Biology
  • Queensland Institute of Medical Research
  • Centre for Advanced Imaging
  • Division of Psychological Medicine and Clinical Neurosciences
  • Cardiff University
  • Duke University
  • Division of Medical Genetics
  • University of Bonn
  • Department of Genomics
  • Erasmus University Rotterdam
  • Department of Psychiatry
  • Dokuz Eylul University
  • Department of Psychiatry
  • Neuroscience and Mental Health
  • Bioinformatics
  • University of British Columbia
  • Department of Epidemiology
  • Harvard University
  • Massachusetts Institute of Technology
  • University of Basel
  • Human Genomics Research Group
  • Department of Genetic Epidemiology in Psychiatry
  • Heidelberg University 

Research output: Contribution to journal › Article › peer-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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