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. 2018 Oct 8:1:163.
doi: 10.1038/s42003-018-0155-y. eCollection 2018.

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

Simone de Jong  1   2 , Mateus Jose Abdalla Diniz  3   4 , Andiara Saloma  3   4 , Ary Gadelha  3 , Marcos L Santoro  5 , Vanessa K Ota  3   5 , Cristiano Noto  3 ; Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium; Charles Curtis  1   2 , Stephen J Newhouse  2   6   7 , Hamel Patel  2   6 , Lynsey S Hall  8 , Paul F O Reilly  1 , Sintia I Belangero  3   5 , Rodrigo A Bressan  3 , Gerome Breen  9   10
Collaborators, Affiliations

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

Simone de Jong et al. Commun Biol. .

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.

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Conflict of interest statement

G.B. has been a consultant in preclinical genomics and has received grant funding from Eli Lilly ltd within the last 3 years. A.G. has participated in advisory boards for Janssen-Cilag and Daiichi-Sankyo. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Violin plots of SCZ:PRS (dark blue plots) MDD:PRS (light blue plots) and BPD:PRS (green plots) for offspring of all spouse pair possibilities. The first category represents PRS in individuals with no affected parents, the next for individuals with an affected family member parent, followed by offspring of an affected married-in individual, and finally offspring of two affected parents. The last two sets of violin plots represent offspring of unknown spouse pairs and the BRA controls. The dot and error bars represent mean ± standard deviation of standardized PRSs
Fig. 2
Fig. 2
Violin plots of SCZ:PRS, MDD:PRS and BPD:PRS per generation for family members only, with results for the generations G3 (n = 25, orange plots), G4 (n = 72, light blue plots), G5 (n = 80, pink plots), and G6 (n = 16, dark purple plots) (excluding the oldest generation G2 and youngest generation G7 because of n = 2 sample size). The dot and error bars represent mean ± standard deviation of standardized PRSs
See this image and copyright information in PMC

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