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 |
Journal | Communications Biology |
Volume | 1 |
Issue number | 1 |
DOIs | |
State | Published - Dec 1 2018 |
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In: Communications Biology, Vol. 1, No. 1, 163, 01.12.2018.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
AU - Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium
AU - de Jong, Simone
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.
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
AU - Hottenga, Jouke Jan
AU - Hougaard, David M.
AU - Ising, Marcus
AU - Jansen, Rick
AU - Jones, Ian
AU - Jones, Lisa A.
AU - Jorgenson, Eric
AU - Knowles, James A.
AU - Kohane, Isaac S.
AU - Kraft, Julia
AU - Kretzschmar, Warren W.
AU - Krogh, Jesper
AU - Kutalik, Zoltán
AU - Li, Yihan
AU - Lind, Penelope A.
AU - MacIntyre, Donald J.
AU - MacKinnon, Dean F.
AU - Maier, Robert M.
AU - Maier, Wolfgang
AU - Marchini, Jonathan
AU - Mbarek, Hamdi
AU - McGrath, Patrick
AU - McGuffin, Peter
AU - Medland, Sarah E.
AU - Mehta, Divya
AU - Middeldorp, Christel M.
AU - Mihailov, Evelin
AU - Milaneschi, Yuri
AU - Milani, Lili
AU - Mondimore, Francis M.
AU - Montgomery, Grant W.
AU - Mostafavi, Sara
AU - Mullins, Niamh
AU - Nauck, Matthias
AU - Ng, Bernard
AU - Nivard, Michel G.
AU - Nyholt, Dale R.
AU - Oskarsson, Hogni
AU - Owen, Michael J.
AU - Painter, Jodie N.
AU - Pedersen, Carsten Bøcker
AU - Pedersen, Marianne Giørtz
AU - Peterson, Roseann E.
AU - Pettersson, Erik
AU - Peyrot, Wouter J.
AU - Pistis, Giorgio
AU - Posthuma, Danielle
AU - Quiroz, Jorge A.
AU - Qvist, Per
AU - Rice, John P.
AU - Riley, Brien P.
AU - Rivera, Margarita
AU - Mirza, Saira Saeed
AU - Schoevers, Robert
AU - Schulte, Eva C.
AU - Shen, Ling
AU - Shyn, Stanley I.
AU - Sigurdsson, Engilbert
AU - Sinnamon, Grant C.B.
AU - Smit, Johannes H.
AU - Smith, Daniel J.
AU - Stefansson, Hreinn
AU - Steinberg, Stacy
AU - Streit, Fabian
AU - Strohmaier, Jana
AU - Tansey, Katherine E.
AU - Teismann, Henning
AU - Teumer, Alexander
AU - Thompson, Wesley
AU - Thomson, Pippa A.
AU - Thorgeirsson, Thorgeir E.
AU - Traylor, Matthew
AU - Treutlein, Jens
AU - Trubetskoy, Vassily
AU - Uitterlinden, André G.
AU - Umbricht, Daniel
AU - Van der Auwera, Sandra
AU - van Hemert, Albert M.
AU - Viktorin, Alexander
AU - Visscher, Peter M.
AU - Wang, Yunpeng
AU - Webb, Bradley T.
AU - Weinsheimer, Shantel Marie
AU - Wellmann, Jürgen
AU - Willemsen, Gonneke
AU - Witt, Stephanie H.
AU - Wu, Yang
AU - Xi, Hualin S.
AU - Yang, Jian
AU - Zhang, Futao
AU - Arolt, Volker
AU - Baune, Bernhard T.
AU - Berger, Klaus
AU - Boomsma, Dorret I.
AU - Cichon, Sven
AU - Dannlowski, Udo
AU - de Geus, E. J.C.
AU - DePaulo, J. Raymond
AU - Domenici, Enrico
AU - Domschke, Katharina
AU - Esko, Tõnu
AU - Grabe, Hans J.
AU - Hamilton, Steven P.
AU - Hayward, Caroline
AU - Heath, Andrew C.
AU - Kendler, Kenneth S.
AU - Kloiber, Stefan
AU - Lewis, Glyn
AU - Li, Qingqin S.
AU - Lucae, Susanne
AU - Madden, Pamela A.F.
AU - Magnusson, Patrik K.
AU - Martin, Nicholas G.
AU - McIntosh, Andrew M.
AU - Metspalu, Andres
AU - Mors, Ole
AU - Mortensen, Preben Bo
AU - Müller-Myhsok, Bertram
AU - Nordentoft, Merete
AU - Nöthen, Markus M.
AU - O’Donovan, Michael C.
AU - Paciga, Sara A.
AU - Pedersen, Nancy L.
AU - Penninx, Brenda W.J.H.
AU - Perlis, Roy H.
AU - Porteous, David J.
AU - Potash, James B.
AU - Preisig, Martin
AU - Rietschel, Marcella
AU - Schaefer, Catherine
AU - Schulze, Thomas G.
AU - Smoller, Jordan W.
AU - Stefansson, Kari
AU - Tiemeier, Henning
AU - Uher, Rudolf
AU - Völzke, Henry
AU - Weissman, Myrna M.
AU - Werge, Thomas
AU - Lewis, Cathryn M.
AU - Levinson, Douglas F.
N1 - Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2018, The Author(s).
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 -