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; Abdel Abdellaoui; Aartjan T.F. Beekman; Conor V. Dolan; Jouke Jan Hottenga; Rick Jansen; Hamdi Mbarek; Yuri Milaneschi; Michel G. Nivard; Danielle Posthuma; Dorret I. Boomsma; E. J.C. de Geus; 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

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, Abdel Abdellaoui, Aartjan T.F. Beekman, Conor V. Dolan, Jouke Jan Hottenga, Rick Jansen, Hamdi Mbarek, Yuri Milaneschi, Michel G. Nivard, Danielle Posthuma, Dorret I. Boomsma, E. J.C. de Geus, Charles Curtis, Stephen J. NewhouseHamel 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

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-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 language	English
Article number	163
Pages (from-to)	1-10
Number of pages	10
Journal	Communications biology
Volume	1
DOIs	https://doi.org/10.1038/s42003-018-0155-y
Publication status	Published - 8 Oct 2018

Funding

We would like to thank the family members for their enthusiastic participation. We thank our ethics consultant Prof. Barbara Prainsack for insightful discussions. This paper represents independent research part-funded by FAPESP (2014/50830-2; 2010/08968-6), the Marie Curie International Research Staff Exchange (FP7-PEOPLE-2011-IRSES/ 295192), and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. SDJ is funded by the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant IF 658195. S.J.N. is also supported by the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, and by awards establishing the Farr Institute of Health Informatics Research at UCLPartners, from the Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institute for Social Care and Health Research, and Wellcome Trust (grant MR/K006584/1). The views expressed are those of the authors and not necessarily those of the EU, the NHS, the NIHR or the Department of Health. Competing Interests: 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.

Funders	Funder number
Marie Curie International Research Staff Exchange	FP7-PEOPLE-2011-IRSES/ 295192
National Institute of Mental Health	U01MH109536
Eli Lilly and Company
National Institute for Social Care and Health Research
King’s College London
South London and Maudsley NHS Foundation Trust
Wellcome Trust	MR/K006584/1
Horizon 2020 Framework Programme	IF 658195
Medical Research Council
Engineering and Physical Sciences Research Council
National Institute for Health Research
British Heart Foundation
Cancer Research UK
Arthritis Research UK
Chief Scientist Office
Fundação de Amparo à Pesquisa do Estado de São Paulo	2014/50830-2, 2010/08968-6
UCLH Biomedical Research Centre

Cohort Studies

Netherlands Twin Register (NTR)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s42003-018-0155-y

Persistent URL (handle)

Persistent link

Cite this

de Jong, S., Diniz, M. J. A., Saloma, A., Gadelha, A., Santoro, M. L., Ota, V. K., Noto, C., Abdellaoui, A., Beekman, A. T. F., Dolan, C. V., Hottenga, J. J., Jansen, R., Mbarek, H., Milaneschi, Y., Nivard, M. G., Posthuma, D., Boomsma, D. I., de Geus, E. J. C., Curtis, C., ... 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. Article 163. https://doi.org/10.1038/s42003-018-0155-y

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year = "2018",

month = oct,

day = "8",

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

language = "English",

volume = "1",

pages = "1--10",

journal = "Communications biology",

issn = "2399-3642",

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de Jong, S, Diniz, MJA, Saloma, A, Gadelha, A, Santoro, ML, Ota, VK, Noto, C, Abdellaoui, A, Beekman, ATF, Dolan, CV , Hottenga, JJ , Jansen, R, Mbarek, H, Milaneschi, Y, Nivard, MG , Posthuma, D , Boomsma, DI , de Geus, EJC, 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

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T1 - Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

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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 - Wray, Naomi R.

AU - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

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AU - Air, Tracy M.

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AU - Cai, Na

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AU - Coleman, Jonathan R.I.

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AU - Craddock, Nick

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AU - Davies, Gail

AU - Deary, Ian J.

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AU - Owen, Michael J.

AU - Painter, Jodie N.

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AU - Levinson, Douglas F.

AU - Børglum, Anders D.

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AU - Xu, Wei

AU - Vincent, John B.

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AU - O’Dushlaine, Colm

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AU - Scott, Laura J.

AU - Flickinger, Matthew

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AU - Guan, Weihua

AU - Absher, Devin

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AU - Frisén, Louise

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AU - Fischer, Sascha B.

AU - Reinbold, Céline S.

AU - Kittel-Schneider, Sarah

AU - Fullerton, Janice M.

AU - Oruč, Lilijana

AU - Para, José G.

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AU - Szelinger, Szabolcs

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AU - Fraser, Christine

AU - Green, Elaine K.

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AU - Collier, David A.

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AU - Young, Allan H.

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AU - Milanova, Vihra

AU - Alda, Martin

AU - Cervantes, Pablo

AU - Cruceanu, Cristiana

AU - Rouleau, Guy A.

AU - Turecki, Gustavo

AU - Paciga, Sara

AU - Winslow, Ashley R.

AU - Grigoroiu-Serbanescu, Maria

AU - Ophoff, Roel

AU - Adolfsson, Rolf

AU - Adolfsson, Annelie Nordin

AU - Del-Favero, Jurgen

AU - Pato, Carlos

AU - Biernacka, Joanna M.

AU - Frye, Mark A.

AU - Morris, Derek

AU - Schork, Nicholas J.

AU - Reif, Andreas

AU - Lissowska, Jolanta

AU - Hauser, Joanna

AU - Szeszenia-Dabrowska, Neonila

AU - McGhee, Kevin

AU - Quinn, Emma

AU - Moskvina, Valentina

AU - Holmans, Peter A.

AU - Farmer, Anne

AU - Kennedy, James L.

AU - Andreassen, Ole A.

AU - Mattingsdal, Morten

AU - Gill, Michael

AU - Bass, Nicholas J.

AU - Gurling, Hugh

AU - McQuillin, Andrew

AU - Breuer, René

AU - Hultman, Christina

AU - Lichtenstein, Paul

AU - Huckins, Laura M.

AU - Leboyer, Marion

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

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

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.

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

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

U2 - 10.1038/s42003-018-0155-y

DO - 10.1038/s42003-018-0155-y

M3 - Article

C2 - 30320231

SN - 2399-3642

VL - 1

SP - 1

EP - 10

JO - Communications biology

JF - Communications biology

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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UN SDGs

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