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

Simone de Jong, Mateus Jose Abdalla Diniz, Andiara Saloma, Ary Gadelha, Marcos L. Santoro, Vanessa K. Ota, Cristiano Noto, Charles Curtis, Stephen J. Newhouse, Hamel Patel, Lynsey S. Hall, Paul F. O`Reilly, Sintia I. Belangero, Rodrigo A. Bressan, Gerome Breen, Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium

Research output: Contribution to JournalArticleAcademicpeer-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
Pages (from-to)1-10
Number of pages10
JournalCommunications biology
Volume1
DOIs
Publication statusPublished - 8 Oct 2018

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behavior disorders
Major Depressive Disorder
Bipolar Disorder
Psychiatry
Pedigree
pedigree
Inborn Genetic Diseases
assortative mating
Pathology
emotions
Mood Disorders
Joints
Observation

Cite this

de Jong, S., Diniz, M. J. A., Saloma, A., Gadelha, A., Santoro, M. L., Ota, V. K., ... Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium (2018). Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder. Communications biology, 1, 1-10. [163]. https://doi.org/10.1038/s42003-018-0155-y
de Jong, Simone ; Diniz, Mateus Jose Abdalla ; Saloma, Andiara ; Gadelha, Ary ; Santoro, Marcos L. ; Ota, Vanessa K. ; Noto, Cristiano ; Curtis, Charles ; Newhouse, Stephen J. ; Patel, Hamel ; Hall, Lynsey S. ; O`Reilly, Paul F. ; Belangero, Sintia I. ; Bressan, Rodrigo A. ; Breen, Gerome ; Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium. / Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder. In: Communications biology. 2018 ; Vol. 1. pp. 1-10.
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de Jong, S, Diniz, MJA, Saloma, A, Gadelha, A, Santoro, ML, Ota, VK, Noto, C, Curtis, C, Newhouse, SJ, Patel, H, Hall, LS, O`Reilly, PF, Belangero, SI, Bressan, RA, Breen, G & Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium 2018, 'Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder' Communications biology, vol. 1, 163, pp. 1-10. https://doi.org/10.1038/s42003-018-0155-y

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder. / de Jong, Simone; Diniz, Mateus Jose Abdalla; Saloma, Andiara; Gadelha, Ary; Santoro, Marcos L.; Ota, Vanessa K.; Noto, Cristiano; Curtis, Charles; Newhouse, Stephen J.; Patel, Hamel; Hall, Lynsey S.; O`Reilly, Paul F.; Belangero, Sintia I.; Bressan, Rodrigo A.; Breen, Gerome; Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium.

In: Communications biology, Vol. 1, 163, 08.10.2018, p. 1-10.

Research output: Contribution to JournalArticleAcademicpeer-review

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PY - 2018/10/8

Y1 - 2018/10/8

N2 - 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.

AB - 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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U2 - 10.1038/s42003-018-0155-y

DO - 10.1038/s42003-018-0155-y

M3 - Article

VL - 1

SP - 1

EP - 10

JO - Communications biology

JF - Communications biology

SN - 2399-3642

M1 - 163

ER -