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

de Jong S, Diniz MJA, Saloma A, Gadelha A, Santoro ML, Ota VK, Noto C, Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, Adams MJ, Agerbo E, Air TM, Andlauer TF, Bacanu SA, Bækvad-Hansen M, Beekman AT, Bigdeli TB, Binder EB, Blackwood DH, Bryois J, Buttenschøn HN, Bybjerg-Grauholm J, Cai N, Castelao E, Christensen JH, Clarke TK, Coleman JR, Colodro-Conde L, Couvy-Duchesne B, Craddock N, Crawford GE, Davies G, Deary IJ, Degenhardt F, Derks EM, Direk N, Dolan CV, Dunn EC, Eley TC, Escott-Price V, Kiadeh FFH, Finucane HK, Forstner AJ, Frank J, Gaspar HA, Gill M, Goes FS, Gordon SD, Grove J, Hansen CS, Hansen TF, Herms S, Hickie IB, Hoffmann P, Homuth G, Horn C, Hottenga JJ, Hougaard DM, Ising M, Jansen R, Jones I, Jones LA, Jorgenson E, Knowles JA, Kohane IS, Kraft J, Kretzschmar WW, Krogh J, Kutalik Z, Li Y, Lind PA, MacIntyre DJ, MacKinnon DF, Maier RM, Maier W, Marchini J, Mbarek H, McGrath P, McGuffin P, Medland SE, Mehta D, Middeldorp CM, Mihailov E, Milaneschi Y, Milani L, Mondimore FM, Montgomery GW, Mostafavi S, Mullins N, Nauck M, Ng B, Nivard MG, Nyholt DR, Oskarsson H, Owen MJ, Painter JN, Pedersen CB, Pedersen MG, Peterson RE, Pettersson E, Peyrot WJ, Pistis G, Posthuma D, Quiroz JA, Qvist P, Rice JP, Riley BP, Rivera M, Mirza SS, Schoevers R, Schulte EC, Shen L, Shyn SI, Sigurdsson E, Sinnamon GC, Smit JH, Smith DJ, Stefansson H, Steinberg S, Streit F, Strohmaier J, Tansey KE, Teismann H, Teumer A, Thompson W, Thomson PA, Thorgeirsson TE, Traylor M, Treutlein J, Trubetskoy V, Uitterlinden AG, Umbricht D, Van der Auwera S, van Hemert AM, Viktorin A, Visscher PM, Wang Y, Webb BT, Weinsheimer SM, Wellmann J, Willemsen G, Witt SH, Wu Y, Xi HS, Yang J, Zhang F, Arolt V, Baune BT, Berger K, Boomsma DI, Cichon S, Dannlowski U, de Geus EJ, DePaulo JR, Domenici E, Domschke K, Esko T, Grabe HJ, Hamilton SP, Hayward C, Heath AC, Kendler KS, Kloiber S, Lewis G, Li QS, Lucae S, Madden PA, Magnusson PK, Martin NG, McIntosh AM, Metspalu A, Mors O, Mortensen PB, Müller-Myhsok B, Nordentoft M, Nöthen MM, O’Donovan MC, Pedersen NL, Penninx BW, Perlis RH, Porteous DJ, Potash JB, Preisig M, Rietschel M, Schaefer C, Schulze TG, Smoller JW, Stefansson K, Tiemeier H, Uher R, Völzke H, Weissman MM, Werge T, Lewis CM, Levinson DF, Børglum AD, Sullivan PF, Meier S, Strauss J, Xu W, Vincent JB, Matthews K, Ferreira M, O’Dushlaine C, Purcell S, Raychaudhuri S, Ruderfer DM, Sklar P, Scott LJ, Flickinger M, Burmeister M, Li J, Guan W, Absher D, Thompson RC, Meng FG, Schatzberg AF, Bunney WE, Barchas JD, Watson SJ, Myers RM, Akil H, Boehnke M, Chambert K, Moran J, Scolnick E, Djurovic S, Melle I, Morken G, Corvin A, Anjorin A, Kandaswamy R, Lawrence J, McLean AW, Pickard BS, Bergen SE, Nimgaonkar V, Landén M, Schalling M, Osby U, Backlund L, Frisén L, Langstrom N, Stahl E, Dobbyn A, Jamain S, Etain B, Bellivier F, Leber M, Maaser A, Fischer SB, Reinbold CS, Kittel-Schneider S, Fullerton JM, Oruč L, Para JG, Mayoral F, Rivas F, Czerski PM, Kammerer-Ciernioch J, Vedder H, Borrmann-Hassenbach M, Pfennig A, Brennan P, McKay JD, Kogevinas M, Schwarz M, Schofield PR, Mühleisen TW, Schumacher J, Bauer M, Wright A, Mitchell PB, Hautzinger M, Kelsoe JR, Greenwood TA, Nievergelt CM, Shilling PD, Smith EN, Bloss CS, Edenberg HJ, Koller DL, Gershon ES, Liu C, Badner JA, Scheftner WA, Lawson WB, Nwulia EA, Hipolito M, Coryell W, Byerley W, McMahon FJ, Lohoff FW, Zandi PP, Mahon PB, McInnis MG, Zöllner S, Zhang P, Szelinger S, St. Clair D, Caesar S, Gordon-Smith K, Fraser C, Green EK, Grozeva D, Hamshere ML, Kirov G, Nikolov I, Collier DA, Elkin A, Williamson R, Young AH, Ferrier IN, Milanova V, Alda M, Cervantes P, Cruceanu C, Rouleau GA, Turecki G, Paciga S, Winslow AR, Grigoroiu-Serbanescu M, Ophoff R, Adolfsson R, Adolfsson AN, Del-Favero J, Pato C, Biernacka JM, Frye MA, Morris D, Schork NJ, Reif A, Lissowska J, Hauser J, Szeszenia-Dabrowska N, McGhee K, Quinn E, Moskvina V, Holmans PA, Farmer A, Kennedy JL, Andreassen OA, Mattingsdal M, Bass NJ, Gurling H, McQuillin A, Breuer R, Hultman C, Lichtenstein P, Huckins LM, Leboyer M, Lathrop M, Nurnberger J, Steffens M, Foroud TM, Berrettini WH, Craig DW, Shi J, Curtis C, Newhouse SJ, Patel H, Hall LS, O`Reilly PF, Belangero SI, Bressan RA, Breen G (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 1

Article Number: 163

Journal Issue: 1

DOI: 10.1038/s42003-018-0155-y

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.

Involved external institutions

University of New South Wales (UNSW) Australia (AU) Eberhard Karls Universität Tübingen Germany (DE) Scripps Research Institute (TSRI) United States (USA) (US) Indiana University – Purdue University Indianapolis United States (USA) (US) University of Chicago United States (USA) (US) Johns Hopkins Hospital United States (USA) (US) King’s College London United Kingdom (GB) University of Dundee United Kingdom (GB) University of Bergen / Universitetet i Bergen Norway (NO) University of Agder / Universitetet i Agder / Agderin yliopisto Norway (NO) University College London (UCL) United Kingdom (GB) Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) Germany (DE) Karolinska Institute Sweden (SE) Lausanne University Hospital / Centre hospitalier universitaire vaudois (CHUV) Switzerland (CH) University of Tartu Estonia (EE) Lundbeck Foundation Initiative for Integrative Psychiatric Research Denmark (DK) Aarhus University Denmark (DK) University of Edinburgh United Kingdom (GB) Max-Planck-Institut für Psychiatrie (Deutsche Forschungsanstalt für Psychiatrie) Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Cardiff University United Kingdom (GB) University of Queensland Australia (AU) Amsterdam University Medical Centers (Amsterdam UMC) / Amsterdam Universitair Medische Centra Netherlands (NL) University of Iowa United States (USA) (US) Duke University United States (USA) (US) Kaiser Permanente United States (USA) (US) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald Germany (DE) Leiden University Medical Center Netherlands (NL) Johns Hopkins University (JHU) United States (USA) (US) Trinity College Dublin Ireland (IE) University of Oxford United Kingdom (GB) Virginia Commonwealth University (VCU) United States (USA) (US) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) University of Amsterdam Netherlands (NL) Columbia University Irving Medical Center (CUIMC) United States (USA) (US) Erasmus University Medical Center (MC) Netherlands (NL) Dalhousie University Canada (CA) University of British Columbia Canada (CA) University of Toronto Canada (CA) F. Hoffmann-La Roche Ltd Switzerland (CH) Princess Margaret Cancer Centre / Princess Margaret Hospital Canada (CA) Centre for Addiction and Mental Health (CAMH) Canada (CA) University of Washington United States (USA) (US) Eli and Edythe L. Broad Institute of MIT and Harvard United States (USA) (US) Icahn School of Medicine at Mount Sinai United States (USA) (US) Harvard University United States (USA) (US) Vanderbilt University United States (USA) (US) Solid Biosciences Inc. United States (USA) (US) University of Michigan United States (USA) (US) Harvard T.H. Chan School of Public Health United States (USA) (US) Washington University in St. Louis United States (USA) (US) HudsonAlpha United States (USA) (US) Wellcome Centre for Human Genetics United Kingdom (GB) Gentofte Hospital Denmark (DK) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen Netherlands (NL) Stanford University United States (USA) (US) University of California Irvine United States (USA) (US) Klinikum der Universität München (LMU Klinikum) Germany (DE) Kaiser Permanente United States (USA) (US) Weill Cornell Medicine United States (USA) (US) Queensland University of Technology (QUT) Australia (AU) University of Iceland (UI) / Háskóli Íslands Iceland (IS) James Cook University Australia (AU) University of Glasgow United Kingdom (GB) deCODE genetics Iceland (IS) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Berkshire Healthcare NHS Foundation Trust United Kingdom (GB) North East London NHS Foundation Trust United Kingdom (GB) Pfizer, Inc. United States (USA) (US) Psychiatrisches Zentrum Nordbaden / Psychiatric Center Nordbaden Germany (DE) Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE) Universitätsspital Basel Switzerland (CH) University of Gothenburg / Göteborgs universitet Sweden (SE) Universidad de Granada Spain (ES) Massachusetts General Hospital United States (USA) (US) University of Adelaide Australia (AU) NTNU Trondheim - Norwegian University of Science and Technology Norway (NO) Institut Mondor de Recherche Biomédicale France (FR) Universitäre Psychiatrische Kliniken Basel (UPK) / Universitäre Psychiatrische Kliniken Base Switzerland (CH) Neuroscience Research Australia NeuRA Australia (AU) Università degli Studi di Trento Italy (IT) Universitätsklinikum Freiburg Germany (DE) Poznan University of Medical Sciences / Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu Poland (PL) Federal University of São Paulo / Universidade Federal de São Paulo (UNIFESP) Brazil (BR) Kliniken des Bezirks Oberbayern (KBO) Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Instituto de Salud Global de Barcelona (ISGlobal) Spain (ES) Forschungszentrum Jülich / Research Centre Jülich (FZJ) Germany (DE) Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) / Federal Institute for Drugs and Medical Devices Germany (DE) University of Pennsylvania (UPenn) United States (USA) (US) Medical University Sofia / Медицински университет Bulgaria (BG) McGill University Health Centre (MUHC) / Centre universitaire de santé McGill Canada (CA) McGill University Canada (CA) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) Umeå University Sweden (SE) University of Antwerp / Universiteit Antwerpen Belgium (BE) Mayo Clinic United States (USA) (US) Keck School of Medicine of USC United States (USA) (US) National Cancer Institute (NCI) United States (USA) (US) University Of Worcester United Kingdom (GB) University of Cambridge United Kingdom (GB) University of Southern California (USC) United States (USA) (US) Charité - Universitätsmedizin Berlin Germany (DE) Institut universitaire de médecine sociale et préventive (IUMSP) Switzerland (CH) University of Sydney (USYD) Australia (AU) Howard University United States (USA) (US) University of California San Francisco (UCSF) United States (USA) (US) National Institute of Mental Health Information Resource Center United States (USA) (US) Universitätsklinikum Köln Germany (DE) University of Minnesota (UMN) United States (USA) (US) University of Pittsburgh United States (USA) (US) Rush University United States (USA) (US) Translational Genomics Research Institute (TGen) United States (USA) (US) University of Aberdeen United Kingdom (GB) University of Birmingham United Kingdom (GB) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Nofer Institute of Occupational Medicine (NIOM) Poland (PL) New South Wales Ministry of Health Australia (AU) Janssen Global Services, LLC United States (USA) (US) Statens Serum Institut Denmark (DK) Wellcome Trust Sanger Institute - Genome Research Limited United Kingdom (GB)

How to cite

APA:

de Jong, S., Diniz, M.J.A., Saloma, A., Gadelha, A., Santoro, M.L., Ota, V.K.,... 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). https://doi.org/10.1038/s42003-018-0155-y

MLA:

de Jong, Simone, et al. "Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder." Communications Biology 1.1 (2018).

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