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

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  • Simone de Jong, King's College London, Storbritannien
  • Mateus Jose Abdalla Diniz, Pax Instituto de Psiquiatria, Brasilien
  • Andiara Saloma, Pax Instituto de Psiquiatria, Brasilien
  • Ary Gadelha, Universidade Federal de Sao Paulo, Brasilien
  • Marcos L Santoro, Universidade Federal de Sao Paulo, Brasilien
  • Vanessa K Ota, Universidade Federal de Sao Paulo, Brasilien
  • Cristiano Noto, Universidade Federal de Sao Paulo, Brasilien
  • Charles Curtis, King's College London, Storbritannien
  • Stephen J Newhouse, University College London, Storbritannien
  • Hamel Patel, King's College London, Storbritannien
  • Lynsey S Hall, Cardiff University, Storbritannien
  • Paul F O Reilly, King's College London, Storbritannien
  • Sintia I Belangero, Universidade Federal de Sao Paulo, Brasilien
  • Rodrigo A Bressan, Universidade Federal de Sao Paulo, Brasilien
  • Gerome Breen, King's College London, Storbritannien
  • Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium (Per Qvist, Preben Bo Mortensen, Henriette Nørmølle Buttenschøn, Jane Hvarregaard Christensen, Jakob Grove, members of -)

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.

OriginalsprogEngelsk
Artikelnummer163
TidsskriftCommunications Biology
Vol/bind1
Nummer1
Antal sider10
ISSN2399-3642
DOI
StatusUdgivet - 2018

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