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Commun Biol. 2018 Oct 8;1:163. doi: 10.1038/s42003-018-0155-y. eCollection 2018.

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

Collaborators (358)

Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, Adams MJ, Agerbo E, Air TM, Andlauer TFM, Bacanu SA, Bækvad-Hansen M, Beekman ATF, Bigdeli TB, Binder EB, Blackwood DHR, Bryois J, Buttenschøn HN, Bybjerg-Grauholm J, Cai N, Castelao E, Christensen JH, Clarke TK, Coleman JRI, 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 GCB, 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 EJC, 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 PAF, Magnusson PK, Martin NG, McIntosh AM, Metspalu A, Mors O, Mortensen PB, Müller-Myhsok B, Nordentoft M, Nöthen MM, O'Donovan MC, Paciga SA, Pedersen NL, Penninx BWJH, 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, Rice J, 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, Gill 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.

Author information

1
1MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, SE5 8AF UK.
2
2National Institute of Health Research Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF UK.
3
3Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, 04021-001 Brazil.
4
Pax Instituto de Psiquiatria, BR153, km 505, Villa Sul V, Aparecida de Goiânia, 74911-516 Brazil.
5
5Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, 04021-001 Brazil.
6
6Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF UK.
7
7Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, London, NW1 2DA UK.
8
8Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, CF10 3AT UK.

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.

Conflict of interest statement

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.

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