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; Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium; Charles Curtis; Stephen J. Newhouse; Hamel Patel; Lynsey S. Hall; Paul F. O`Reilly; Sintia I. Belangero; Rodrigo A. Bressan; Gerome Breen

doi:10.1038/s42003-018-0155-y

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, Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium, Charles Curtis, Stephen J. Newhouse, Hamel Patel, Lynsey S. Hall, Paul F. O`Reilly, Sintia I. Belangero, Rodrigo A. Bressan, Gerome Breen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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 language	English
Article number	163
Journal	Communications Biology
Volume	1
Issue number	1
Early online date	8 Oct 2018
DOIs	https://doi.org/10.1038/s42003-018-0155-y
Publication status	Published - 1 Dec 2018

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10.1038/s42003-018-0155-yLicence: Creative Commons: Attribution (CC-BY)

s42003-018-0155-yFinal published version, 681 KBLicence: Creative Commons: Attribution (CC-BY)

Cite this

de Jong, S., Diniz, M. J. A., Saloma, A., Gadelha, A., Santoro, M. L., Ota, V. K., Noto, C., Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium, Curtis, C., Newhouse, S. J., Patel, H., Hall, L. S., O`Reilly, P. F., Belangero, S. I., Bressan, R. A., & Breen, G. (2018). Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder. Communications Biology, 1(1), Article 163. https://doi.org/10.1038/s42003-018-0155-y

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note = "Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s42003-018-0155-y",

language = "English",

volume = "1",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

}

de Jong, S, Diniz, MJA, Saloma, A, Gadelha, A, Santoro, ML, Ota, VK, Noto, C, Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium, Curtis, C, Newhouse, SJ, Patel, H, Hall, LS, O`Reilly, PF, Belangero, SI, Bressan, RA & Breen, G 2018, 'Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder', Communications Biology, vol. 1, no. 1, 163. https://doi.org/10.1038/s42003-018-0155-y

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AU - Diniz, Mateus Jose Abdalla

AU - Saloma, Andiara

AU - Gadelha, Ary

AU - Santoro, Marcos L.

AU - Ota, Vanessa K.

AU - Noto, Cristiano

AU - Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium

AU - Wray, Naomi R.

AU - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

AU - Adams, Mark J.

AU - Agerbo, Esben

AU - Air, Tracy M.

AU - Andlauer, Till F.M.

AU - Bacanu, Silviu Alin

AU - Bækvad-Hansen, Marie

AU - Beekman, Aartjan T.F.

AU - Bigdeli, Tim B.

AU - Binder, Elisabeth B.

AU - Blackwood, Douglas H.R.

AU - Bryois, Julien

AU - Buttenschøn, Henriette N.

AU - Bybjerg-Grauholm, Jonas

AU - Cai, Na

AU - Castelao, Enrique

AU - Christensen, Jane Hvarregaard

AU - Clarke, Toni Kim

AU - Coleman, Jonathan R.I.

AU - Colodro-Conde, Lucía

AU - Couvy-Duchesne, Baptiste

AU - Craddock, Nick

AU - Crawford, Gregory E.

AU - Davies, Gail

AU - Deary, Ian J.

AU - Degenhardt, Franziska

AU - Derks, Eske M.

AU - Direk, Nese

AU - Dolan, Conor V.

AU - Dunn, Erin C.

AU - Eley, Thalia C.

AU - Escott-Price, Valentina

AU - Kiadeh, Farnush Farhadi Hassan

AU - Finucane, Hilary K.

AU - Forstner, Andreas J.

AU - Frank, Josef

AU - Gaspar, Héléna A.

AU - Gill, Michael

AU - Goes, Fernando S.

AU - Gordon, Scott D.

AU - Grove, Jakob

AU - Hansen, Christine Søholm

AU - Hansen, Thomas F.

AU - Herms, Stefan

AU - Hickie, Ian B.

AU - Hoffmann, Per

AU - Homuth, Georg

AU - Horn, Carsten

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AU - Hougaard, David M.

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AU - Jones, Lisa A.

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AU - Holmans, Peter A.

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AU - Hultman, Christina

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AU - Lathrop, Mark

AU - Nurnberger, John

AU - Steffens, Michael

AU - Foroud, Tatiana M.

AU - Berrettini, Wade H.

AU - Craig, David W.

AU - Shi, Jianxin

AU - Curtis, Charles

AU - Newhouse, Stephen J.

AU - Patel, Hamel

AU - Hall, Lynsey S.

AU - O`Reilly, Paul F.

AU - Belangero, Sintia I.

AU - Bressan, Rodrigo A.

AU - Breen, Gerome

PY - 2018/12/1

Y1 - 2018/12/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85061101811&partnerID=8YFLogxK

U2 - 10.1038/s42003-018-0155-y

DO - 10.1038/s42003-018-0155-y

M3 - Article

C2 - 30320231

AN - SCOPUS:85061101811

SN - 2399-3642

VL - 1

JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 163

ER -

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

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