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

Thomas Mears Werge (Medlem af forfattergruppering), Thomas Folkmann Hansen (Medlem af forfattergruppering), Wesley Kurt Thompson (Medlem af forfattergruppering), Shantel Marie Weinsheimer (Medlem af forfattergruppering), Merete Nordentoft (Medlem af forfattergruppering), Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium (Thomas Werge, Merete Nordentoft, Thomas F. Hansen, Wesley Thompson, Shantel Marie Weinsheimer (Members))

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.

OriginalsprogEngelsk
TidsskriftCommunications biology
Vol/bind1
Sider (fra-til)163
ISSN2399-3642
DOI
StatusUdgivet - 2018

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