| Title: |
Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology |
| Authors: |
Mullins, Niamh; Forstner, Andeas J.; Charney, Alexander W.; Kamatani, Y; Kennedy, JL; Kittel-Schneider, S; Knowles, JA; Kogevinas, M; Koromina, M; Kranz, TM; Kranzler, HR; Kubo, M; Kupka, R; Drange, Ole Kristian; Kushner, SA; Lavebratt, C; Lawrence, J; Leber, M; Lee, H-J; Lee, PH; Levy, SE; Lewis, C; Liao, C; Lucae, S; Gandal, Michael J.; Lundberg, M; MacIntyre, DJ; Maier, W; Maihofer, A; Malaspina, D; Maratou, E; Martinsson, L; Mattheisen, M; McCarroll, SA; McGregor, NW; Hagenaars, Saskia P.; McGuffin, P; McKay, JD; Medeiros, H; Medland, SE; Millischer, V; Montgomery, GW; Moran, JL; Morris, DW; Muhleisen, TW; O'Brien, N; Ikeda, Masashi; O'Donovan, C; Loohuis, LMO; Oruc, L; Papiol, S; Pardinas, AF; Perry, A; Pfennig, A; Porichi, E; Potash, JB; Quested, D; Kamitaki, Nolan; Raj, T; Rapaport, MH; DePaulo, JR; Regeer, EJ; Rice, JP; Rivas, F; Rivera, M; Roth, J; Roussos, P; Ruderfer, DM; Kim, Minsoo; Sanchez-Mora, C; Schulte, EC; Senner, F; Sharp, S; Shilling, PD; Sigurdsson, E; Sirignano, L; Slaney, C; Smeland, OB; Sobell, JL; Krebs, Kristi; Hansen, CS; Artigas, MS; Spijker, AT; Stein, DJ; Strauss, JS; Swiatkowska, B; Terao, C; Thorgeirsson, TE; Toma, C; Tooney, Paul; Panagiotaropoulou, Georgia; Tsermpini, E-E; Vawter, MP; Vedder, H; Walters, JTR; Witt, SH; Xi, S; Xu, W; Yang, JMK; Young, AH; Young, H; Schilder, Brian M.; Zandi, PP; Zhou, H; Zillich, L; Adolfsson, R; Agartz, I; Alda, M; Alfredsson, L; Babadjanova, G; Backlund, L; Baune, BT; O'Connell, Kevin S.; Sloofman, Laura G.; Bellivier, F; Bengesser, S; Berrettini, WH; Blackwood, DHR; Boehnke, M; Borglum, AD; Breen, G; Carr, VJ; Catts, S; Corvin, A; Steinberg, S; Craddock, N; Dannlowski, U; Dikeos, D; Esko, T; Etain, B; Ferentinos, P; Frye, M; Fullerton, JM; Gawlik, M; Gershon, ES; Trubetskoy, V; Goes, F; Green, MJ; Grigoroiu-Serbanescu, M; Hauser, J; Henskens, F; Hillert, J; Hong, KS; Hougaard, DM; Hultman, CM; Hveem, K; Winsvold, BS; Iwata, N; Jablensky, A; Jones, I; Jones, LA; Kahn, RS; Kelsoe, JR; Kirov, G; Landen, M; Leboyer, M; Lewis, CM; Won, H-H; Li, QS; Lissowska, J; Lochner, C; Loughland, Carmel; Martin, NG; Mathews, CA; Mayoral, F; McElroy, SL; McIntosh, AM; McMahon, FJ; Abramova, L; Melle, I; Michie, P; Milani, L; Mitchell, PB; Morken, G; Mors, O; Mortensen, PB; Mowry, B; Muller-Myhsok, B; Myers, RM; Adorjan, K; Neale, BM; Nievergelt, CM; Nordentoft, M; Nothen, MM; ODonovan, MC; Oedegaard, KJ; Olsson, T; Owen, MJ; Paciga, SA; Pantelis, C; Agerbo, E; Pato, C; Pato, MT; Patrinos, GP; Perlis, RH; Posthuma, D; Ramos-Quiroga, JA; Reif, A; Reininghaus, EZ; Ribases, M; Rietschel, M; Al Eissa, M; Ripke, S; Rouleau, GA; Saito, T; Schall, U; Schalling, M; Schofield, PR; Schulze, TG; Scott, LJ; Scott, RJ; Serretti, A; Albani, D; Weickert, CS; Smoller, JW; Stefansson, H; Stefansson, K; Stordal, E; Streit, F; Sullivan, PF; Turecki, G; Vaaler, AE; Vieta, E; Coombes, Brandon; Alliey-Rodriguez, N; Vincent, JB; Waldman, ID; Weickert, TW; Werge, T; Wray, NR; Zwart, J; Biernacka, JM; Nurnberger, J; Cichon, S; Edenberg, HJ; Anjorin, A; Stahl, EA; McQuillin, A; Di Florio, A; Ophoff, RA; Andreassen, OA; Antilla, V; Antoniou, A; Awasthi, S; Baek, JH; Baekvad-Hansen, M; Bass, N; Bauer, M; Beins, EC; Coleman, Jonathan R. I.; Bergen, SE; Birner, A; Pedersen, CB; Boen, E; Boks, MP; Bosch, R; Brum, M; Brumpton, BM; Brunkhorst-Kanaan, N; Budde, M; Qiao, Zhen; Bybjerg-Grauholm, J; Byerley, W; Cairns, Murray; Casas, M; Cervantes, P; Clarke, T-K; Cruceanu, C; Cuellar-Barboza, A; Cunningham, J; Curtis, D; Als, Thomas D.; Czerski, PM; Dale, AM; Dalkner, N; David, FS; Degenhardt, F; Djurovic, S; Dobbyn, AL; Douzenis, A; Elvsashagen, T; Escott-Price, V; Bigdeli, Tim B.; Ferrier, IN; Fiorentino, A; Foroud, TM; Forty, L; Frank, J; Frei, O; Freimer, NB; Frisen, L; Gade, K; Garnham, J; Børte, Sigrid; Gelernter, J; Pedersen, MG; Gizer, IR; Gordon, SD; Gordon-Smith, K; Greenwood, TA; Grove, J; Guzman-Parra, J; Ha, K; Haraldsson, M; Bryois, Julien; Hautzinger, M; Heilbronner, U; Hellgren, D; Herms, S; Hoffmann, P; Holmans, PA; Huckins, L; Jamain, S; Johnson, JS; Kalman, JL |
| Contributors: |
The University of Newcastle. College of Health, Medicine & Wellbeing, School of Biomedical Sciences and Pharmacy |
| Publisher Information: |
Nature Publishing Group |
| Publication Year: |
2021 |
| Collection: |
NOVA: The University of Newcastle Research Online (Australia) |
| Subject Terms: |
bipolar disorder; genome; case-control studies; attention deficit hyperactivity disorder |
| Description: |
Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Nature Genetics Vol. 53, Issue 6, p. 817-829; http://hdl.handle.net/1959.13/1473400; uon:49007 |
| Availability: |
http://hdl.handle.net/1959.13/1473400 |
| Accession Number: |
edsbas.A444A24B |
| Database: |
BASE |