Abstract

Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n?=?158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the ge...

Authors	O'Connell, KS; Koromina, M; van der Veen, T; Boltz, T; David, FS; Yang, JMK; Lin, KH; Wang, X; Coleman, JRI; Mitchell, BL; McGrouther, CC; Rangan, AV; Lind, PA; Koch, E; Harder, A; Parker, N; Bendl, J; Adorjan, K; Agerbo, E; Albani, D; Alemany, S; Alliey-Rodriguez, N; Als, TD; Andlauer, TFM; Antoniou, A; Ask, H; Bass, N; Bauer, M; Beins, EC; Bigdeli, TB; Pedersen, CB; Boks, MP; Børte, S; Bosch, R; Brum, M; Brumpton, BM; Brunkhorst-Kanaan, N; Budde, M; Bybjerg-Grauholm, J; Byerley, W; Cabana-Domínguez, J; Cairns, MJ; Carpiniello, B; Casas, M; Cervantes, P; Chatzinakos, C; Chen, HC; Clarence, T; Clarke, TK; Claus, I; Coombes, B; Corfield, EC; Cruceanu, C; Cuellar-Barboza, A; Czerski, PM; Dafnas, K; Dale, AM; Dalkner, N; Degenhardt, F; DePaulo, JR; Djurovic, S; Drange, OK; Escott-Price, V; Fanous, AH; Fellendorf, FT; Ferrier, IN; Forty, L; Frank, J; Frei, O; Freimer, NB; Fullard, JF; Garnham, J; Gizer, IR; Gordon, SD; Gordon-Smith, K; Greenwood, TA; Grove, J; Guzman-Parra, J; Ha, TH; Hahn, T; Haraldsson, M; Hautzinger, M; Havdahl, A; Heilbronner, U; Hellgren, D; Herms, S; Hickie, IB; Hoffmann, P; Holmans, PA; Huang, MC; Ikeda, M; Jamain, S; Johnson, JS; Jonsson, L; Kalman, JL; Kamatani, Y; Kennedy, JL; Kim, E; Kim, J; Kittel-Schneider, S; Knowles, JA; Kogevinas, M; Kranz, TM; Krebs, K; Kushner, SA; Lavebratt, C; Lawrence, J; Leber, M; Lee, HJ; Liao, C; Lucae, S; Lundberg, M; MacIntyre, DJ; Maier, W; Maihofer, AX; Malaspina, D; Manchia, M; Maratou, E; Martinsson, L; Mattheisen, M; McGregor, NW; McInnis, MG; McKay, JD; Medeiros, H; Meyer-Lindenberg, A; Millischer, V; Morris, DW; Moutsatsou, P; Mühleisen, TW; O'Donovan, C; Olsen, CM; Panagiotaropoulou, G; Papiol, S; Pardiñas, AF; Park, HY; Perry, A; Pfennig, A; Pisanu, C; Potash, JB; Quested, D; Rapaport, MH; Regeer, EJ; Rice, JP; Rivera, M; Schulte, EC; Senner, F; Shadrin, A; Shilling, PD; Sigurdsson, E; Sindermann, L; Sirignano, L; Siskind, D; Slaney, C; Sloofman, LG; Smeland, OB; Smith, DJ; Sobell, JL; Soler Artigas, M; Stein, DJ; Stein, F; Su, MH; Sung, H; Swiatkowska, B; Terao, C; Tesfaye, M; Tesli, M; Thorgeirsson, TE; Thorp, JG; Toma, C; Tondo, L; Tooney, PA; Tsai, SJ; Tsermpini, EE; Vawter, MP; Vedder, H; Vreeker, A; Walters, JTR; Winsvold, BS; Witt, SH; Won, HH; Ye, R; Young, AH; Zandi, PP; Zillich, L; 23andMe Research Team; Adolfsson, R; Alda, M; Alfredsson, L; Backlund, L; Baune, BT; Bellivier, F; Bengesser, S; Berrettini, WH; Biernacka, JM; Boehnke, M; Børglum, AD; Breen, G; Carr, VJ; Catts, S; Cichon, S; Corvin, A; Craddock, N; Dannlowski, U; Dikeos, D; Etain, B; Ferentinos, P; Frye, M; Fullerton, JM; Gawlik, M; Gershon, ES; Goes, FS; Green, MJ; Grigoroiu-Serbanescu, M; Hauser, J; Henskens, FA; Hjerling-Leffler, J; Hougaard, DM; Hveem, K; Iwata, N; Jones, I; Jones, LA; Kahn, RS; Kelsoe, JR; Kircher, T; Kirov, G; Kuo, PH; Landén, M; Leboyer, M; Li, QS; Lissowska, J; Lochner, C; Loughland, C; Luykx, JJ; Martin, NG; Mathews, CA; Mayoral, F; McElroy, SL; McIntosh, AM; McMahon, FJ; Medland, SE; Melle, I; Milani, L; Mitchell, PB; Morken, G; Mors, O; Mortensen, PB; Müller-Myhsok, B; Myers, RM; Myung, W; Neale, BM; Nievergelt, CM; Nordentoft, M; Nöthen, MM; Nurnberger, JI; O'Donovan, MC; Oedegaard, KJ; Olsson, T; Owen, MJ; Paciga, SA; Pantelis, C; Pato, CN; Pato, MT; Patrinos, GP; Pawlak, JM; Ramos-Quiroga, JA; Reif, A; Reininghaus, EZ; Ribasés, M; Rietschel, M; Ripke, S; Rouleau, GA; Roussos, P; Saito, T; Schall, U; Schalling, M; Schofield, PR; Schulze, TG; Scott, LJ; Scott, RJ; Serretti, A; Smoller, JW; Squassina, A; Stahl, EA; Stefansson, H; Stefansson, K; Stordal, E; Streit, F; Sullivan, PF; Turecki, G; Vaaler, AE; Vieta, E; Vincent, JB; Waldman, ID; Weickert, CS; Weickert, TW; Werge, T; Whiteman, DC; Zwart, JA; Edenberg, HJ; McQuillin, A; Forstner, AJ; Mullins, N; Di Florio, A; Ophoff, RA; Andreassen, OA; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium
Journal	NATURE
Pages
Volume
Date	22/03/2025
Grant ID
Funding Body
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/s41586-024-08468-9