The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls
Coleman JR, Gaspar HA, Bryois J, Byrne EM, Forstner AJ, Holmans PA, de Leeuw CA, Mattheisen M, McQuillin A, Whitehead Pavlides JM, Pers TH, Ripke S, Stahl EA, Steinberg S, Trubetskoy V, Trzaskowski M, Wang Y, Abbott L, Abdellaoui A, Adams MJ, Adolfsson AN, Agerbo E, Akil H, Albani D, Alliey-Rodriguez N, Als TD, Andlauer TF, Anjorin A, Antilla V, Van der Auwera S, Awasthi S, Bacanu SA, Badner JA, Bækvad-Hansen M, Barchas JD, Bass N, Bauer M, Beekman AT, Belliveau R, Bergen SE, Bigdeli TB, Binder EB, Bøen E, Boks M, Boocock J, Budde M, Bunney W, Burmeister M, Buttenschøn HN, Bybjerg-Grauholm J, Byerley W, Cai N, Casas M, Castelao E, Cerrato F, Cervantes P, Chambert K, Charney AW, Chen D, Christensen JH, Churchhouse C, St Clair D, Clarke TK, Colodro-Conde L, Coryell W, Couvy-Duchesne B, Craig DW, Crawford GE, Cruceanu C, Czerski PM, Dale AM, Davies G, Deary IJ, Degenhardt F, Del-Favero J, DePaulo JR, Derks EM, Direk N, Djurovic S, Dobbyn AL, Dolan CV, Dumont A, Dunn EC, Eley TC, Elvsåshagen T, Escott-Price V, Fan CC, Finucane HK, Fischer SB, Flickinger M, Foo JC, Foroud TM, Forty L, Frank J, Fraser C, Freimer NB, Frisén L, Gade K, Gage D, Garnham J, Giambartolomei C, Goes FS, Goldstein J, Gordon SD, Gordon-Smith K, Green EK, Green MJ, Greenwood TA, Grove J, Guan W, Hall LS, Hamshere ML, Hansen CS, Hansen TF, Hautzinger M, Heilbronner U, van Hemert AM, Herms S, Hickie IB, Hipolito M, Hoffmann P, Holland D, Homuth G, Horn C, Hottenga JJ, Huckins L, Ising M, Jamain S, Jansen R, Johnson JS, de Jong S, Jorgenson E, Juréus A, Kandaswamy R, Karlsson R, Kennedy JL, Hassan Kiadeh FF, Kittel-Schneider S, Knowles JA, Kogevinas M, Kohane IS, Koller AC, Kraft J, Kretzschmar WW, Krogh J, Kupka R, Kutalik Z, Lavebratt C, Lawrence J, Lawson WB, Leber M, Lee PH, Levy SE, Li JZ, Li Y, Lind PA, Liu C, Olde Loohuis LM, Maaser A, MacIntyre DJ, MacKinnon DF, Mahon PB, Maier W, Maier RM, Marchini J, Martinsson L, Mbarek H, McCarroll S, McGrath P, McGuffin P, McInnis MG, McKay JD, Medeiros H, Medland SE, Mehta D, Meng F, Middeldorp CM, Mihailov E, Milaneschi Y, Milani L, Mirza SS, Mondimore FM, Montgomery GW, Morris DW, Mostafavi S, Mühleisen TW, Mullins N, Nauck M, Ng B, Nguyen H, Nievergelt CM, Nivard MG, Nwulia EA, Nyholt DR, O'Donovan C, O'Reilly PF, Ori AP, Oruc L, Ösby U, Oskarsson H, Painter JN, Parra JG, Pedersen CB, Pedersen MG, Perry A, Peterson RE, Pettersson E, Peyrot WJ, Pfennig A, Pistis G, Purcell SM, Quiroz JA, Qvist P, Regeer EJ, Reif A, Reinbold CS, Rice JP, Riley BP, Rivas F, Rivera M, Roussos P, Ruderfer DM, Ryu E, Sánchez-Mora C, Schatzberg AF, Scheftner WA, Schoevers R, Schork NJ, Schulte EC, Shehktman T, Shen L, Shi J, Shilling PD, Shyn SI, Sigurdsson E, Slaney C, Smeland OB, Smit JH, Smith DJ, Sobell JL, Spijker AT, Steffens M, Strauss JS, Streit F, Strohmaier J, Szelinger S, Tansey KE, Teismann H, Teumer A, Thompson RC, Thompson W, Thomson PA, Thorgeirsson TE, Traylor M, Treutlein J, Uitterlinden AG, Umbricht D, Vedder H, Viktorin A, Visscher PM, Wang W, Watson SJ, Webb BT, Weickert CS, Weickert TW, Weinsheimer SM, Wellmann J, Willemsen G, Witt SH, Wu Y, Xi HS, Xu W, Yang J, Young AH, Zandi P, Zhang P, Zhang F, Zollner S, Adolfsson R, Agartz I, Alda M, Arolt V, Backlund L, Baune BT, Bellivier F, Berger K, Berrettini WH, Biernacka JM, Blackwood DH, Boehnke M, Boomsma DI, Corvin A, Craddock N, Daly MJ, Dannlowski U, Domenici E, Domschke K, Esko T, Etain B, Frye M, Fullerton JM, Gershon ES, de Geus EJ, Gill M, Goes F, Grabe HJ, Grigoroiu-Serbanescu M, Hamilton SP, Hauser J, Hayward C, Heath AC, Hougaard DM, Hultman CM, Jones I, Jones LA, Kahn RS, Kendler KS, Kirov G, Kloiber S, Landén M, Leboyer M, Lewis G, Li QS, Lissowska J, Lucae S, Madden PA, Magnusson PK, Martin NG, Mayoral F, McElroy SL, McIntosh AM, McMahon FJ, Melle I, Metspalu A, Mitchell PB, Morken G, Mors O, Mortensen PB, Müller-Myhsok B, Myers RM, Neale BM, Nimgaonkar V, Nordentoft M, Nöthen MM, O'Donovan MC, Oedegaard KJ, Owen MJ, Paciga SA, Pato C, Pato MT, Pedersen NL, Penninx BW, Perlis RH, Porteous DJ, Posthuma D, Potash JB, Preisig M, Ramos-Quiroga JA, Ribasés M, Rietschel M, Rouleau GA, Schaefer C, Schalling M, Schofield PR, Schulze TG, Serretti A, Smoller JW, Stefansson H, Stefansson K, Stordal E, Tiemeier H, Turecki G, Uher R, Vaaler AE, Vieta E, Vincent JB, Völzke H, Weissman MM, Werge T, Andreassen OA, Børglum AD, Cichon S, Edenberg HJ, Di Florio A, Kelsoe J, Levinson DF, Lewis CM, Nurnberger JI, Ophoff RA, Scott LJ, Sklar P, Sullivan PF, Wray NR, Breen G (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 88
Pages Range: 169-184
Journal Issue: 2
DOI: 10.1016/j.biopsych.2019.10.015
Abstract
Background: Mood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction. Methods: To clarify the shared molecular genetic basis of major depressive disorder and bipolar disorder and to highlight disorder-specific associations, we meta-analyzed data from the latest Psychiatric Genomics Consortium genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; nonoverlapping N = 609,424). Results: Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More loci from the Psychiatric Genomics Consortium analysis of major depression than from that for bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single-episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment—the relationship is positive in bipolar disorder but negative in major depressive disorder. Conclusions: The mood disorders share several genetic associations, and genetic studies of major depressive disorder and bipolar disorder can be combined effectively to enable the discovery of variants not identified by studying either disorder alone. However, we demonstrate several differences between these disorders. Analyzing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.
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APA:
Coleman, J.R., Gaspar, H.A., Bryois, J., Byrne, E.M., Forstner, A.J., Holmans, P.A.,... Breen, G. (2020). The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls. Biological Psychiatry, 88(2), 169-184. https://doi.org/10.1016/j.biopsych.2019.10.015
MLA:
Coleman, Jonathan R.I., et al. "The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls." Biological Psychiatry 88.2 (2020): 169-184.
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