@article{3076242,
    title = "Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology",
    author = "Mullins, N. and Forstner, A.J. and O’Connell, K.S. and Coombes, B. and Coleman, J.R.I. and Qiao, Z. and Als, T.D. and Bigdeli, T.B. and Børte, S. and Bryois, J. and Charney, A.W. and Drange, O.K. and Gandal, M.J. and Hagenaars, S.P. and Ikeda, M. and Kamitaki, N. and Kim, M. and Krebs, K. and Panagiotaropoulou, G. and Schilder, B.M. and Sloofman, L.G. and Steinberg, S. and Trubetskoy, V. and Winsvold, B.S. and Won, H.-H. and Abramova, L. and Adorjan, K. and Agerbo, E. and Al Eissa, M. and Albani, D. and Alliey-Rodriguez, N. and Anjorin, A. and Antilla, V. and Antoniou, A. and Awasthi, S. and Baek, J.H. and Bækvad-Hansen, M. and Bass, N. and Bauer, M. and Beins, E.C. and Bergen, S.E. and Birner, A. and Bøcker Pedersen, C. and Bøen, E. and Boks, M.P. and Bosch, R. and Brum, M. and Brumpton, B.M. and Brunkhorst-Kanaan, N. and Budde, M. and Bybjerg-Grauholm, J. and Byerley, W. and Cairns, M. and Casas, M. and Cervantes, P. and Clarke, T.-K. and Cruceanu, C. and Cuellar-Barboza, A. and Cunningham, J. and Curtis, D. and Czerski, P.M. and Dale, A.M. and Dalkner, N. and David, F.S. and Degenhardt, F. and Djurovic, S. and Dobbyn, A.L. and Douzenis, A. and Elvsåshagen, T. and Escott-Price, V. and Ferrier, I.N. and Fiorentino, A. and Foroud, T.M. and Forty, L. and Frank, J. and Frei, O. and Freimer, N.B. and Frisén, L. and Gade, K. and Garnham, J. and Gelernter, J. and Giørtz Pedersen, M. and Gizer, I.R. and Gordon, S.D. and Gordon-Smith, K. and Greenwood, T.A. and Grove, J. and Guzman-Parra, J. and Ha, K. and Haraldsson, M. and Hautzinger, M. and Heilbronner, U. and Hellgren, D. and Herms, S. and Hoffmann, P. and Holmans, P.A. and Huckins, L. and Jamain, S. and Johnson, J.S. and Kalman, J.L. and Kamatani, Y. and Kennedy, J.L. and Kittel-Schneider, S. and Knowles, J.A. and Kogevinas, M. and Koromina, M. and Kranz, T.M. and Kranzler, H.R. and Kubo, M. and Kupka, R. and Kushner, S.A. and Lavebratt, C. and Lawrence, J. and Leber, M. and Lee, H.-J. and Lee, P.H. and Levy, S.E. and Lewis, C. and Liao, C. and Lucae, S. and Lundberg, M. and MacIntyre, D.J. and Magnusson, S.H. and Maier, W. and Maihofer, A. and Malaspina, D. and Maratou, E. and Martinsson, L. and Mattheisen, M. and McCarroll, S.A. and McGregor, N.W. and McGuffin, P. and McKay, J.D. and Medeiros, H. and Medland, S.E. and Millischer, V. and Montgomery, G.W. and Moran, J.L. and Morris, D.W. and Mühleisen, T.W. and O’Brien, N. and O’Donovan, C. and Olde Loohuis, L.M. and Oruc, L. and Papiol, S. and Pardiñas, A.F. and Perry, A. and Pfennig, A. and Porichi, E. and Potash, J.B. and Quested, D. and Raj, T. and Rapaport, M.H. and DePaulo, J.R. and Regeer, E.J. and Rice, J.P. and Rivas, F. and Rivera, M. and Roth, J. and Roussos, P. and Ruderfer, D.M. and Sánchez-Mora, C. and Schulte, E.C. and Senner, F. and Sharp, S. and Shilling, P.D. and Sigurdsson, E. and Sirignano, L. and Slaney, C. and Smeland, O.B. and Smith, D.J. and Sobell, J.L. and Søholm Hansen, C. and Soler Artigas, M. and Spijker, A.T. and Stein, D.J. and Strauss, J.S. and Świątkowska, B. and Terao, C. and Thorgeirsson, T.E. and Toma, C. and Tooney, P. and Tsermpini, E.-E. and Vawter, M.P. and Vedder, H. and Walters, J.T.R. and Witt, S.H. and Xi, S. and Xu, W. and Yang, J.M.K. and Young, A.H. and Young, H. and Zandi, P.P. and Zhou, H. and Zillich, L. and Adolfsson, R. and Agartz, I. and Alda, M. and Alfredsson, L. and Babadjanova, G. and Backlund, L. and Baune, B.T. and Bellivier, F. and Bengesser, S. and Berrettini, W.H. and Blackwood, D.H.R. and Boehnke, M. and Børglum, A.D. and Breen, G. and Carr, V.J. and Catts, S. and Corvin, A. and Craddock, N. and Dannlowski, U. and Dikeos, D. and Esko, T. and Etain, B. and Ferentinos, P. and Frye, M. and Fullerton, J.M. and Gawlik, M. and Gershon, E.S. and Goes, F.S. and Green, M.J. and Grigoroiu-Serbanescu, M. and Hauser, J. and Henskens, F. and Hillert, J. and Hong, K.S. and Hougaard, D.M. and Hultman, C.M. and Hveem, K. and Iwata, N. and Jablensky, A.V. and Jones, I. and Jones, L.A. and Kahn, R.S. and Kelsoe, J.R. and Kirov, G. and Landén, M. and Leboyer, M. and Lewis, C.M. and Li, Q.S. and Lissowska, J. and Lochner, C. and Loughland, C. and Martin, N.G. and Mathews, C.A. and Mayoral, F. and McElroy, S.L. and McIntosh, A.M. and McMahon, F.J. and Melle, I. and Michie, P. and Milani, L. and Mitchell, P.B. and Morken, G. and Mors, O. and Mortensen, P.B. and Mowry, B. and Müller-Myhsok, B. and Myers, R.M. and Neale, B.M. and Nievergelt, C.M. and Nordentoft, M. and Nöthen, M.M. and O’Donovan, M.C. and Oedegaard, K.J. and Olsson, T. and Owen, M.J. and Paciga, S.A. and Pantelis, C. and Pato, C. and Pato, M.T. and Patrinos, G.P. and Perlis, R.H. and Posthuma, D. and Ramos-Quiroga, J.A. and Reif, A. and Reininghaus, E.Z. and Ribasés, M. and Rietschel, M. and Ripke, S. and Rouleau, G.A. and Saito, T. and Schall, U. and Schalling, M. and Schofield, P.R. and Schulze, T.G. and Scott, L.J. and Scott, R.J. and Serretti, A. and Shannon Weickert, C. and Smoller, J.W. and Stefansson, H. and Stefansson, K. and Stordal, E. and Streit, F. and Sullivan, P.F. and Turecki, G. and Vaaler, A.E. and Vieta, E. and Vincent, J.B. and Waldman, I.D. and Weickert, T.W. and Werge, T. and Wray, N.R. and Zwart, J.-A. and Biernacka, J.M. and Nurnberger, J.I. and Cichon, S. and Edenberg, H.J. and Stahl, E.A. and McQuillin, A. and Di Florio, A. and Ophoff, R.A. and Andreassen, O.A. and HUNT All-In Psychiatry",
    journal = "Nature Genetics",
    year = "2021",
    volume = "53",
    number = "6",
    pages = "817-829",
    publisher = "Lithuanian Nature Research Centre",
    issn = "1061-4036, 1546-1718",
    doi = "10.1038/s41588-021-00857-4",
    keywords = "anesthetic agent;  anticonvulsive agent;  anxiolytic agent;  calcium channel blocking agent;  hypnotic sedative agent;  neuroleptic agent, alcohol abuse;  allele;  anorexia;  Article;  attention deficit hyperactivity disorder;  autism;  bipolar disorder;  cohort analysis;  controlled study;  daytime somnolence;  expression quantitative trait locus;  female;  gene expression;  gene linkage disequilibrium;  genetic correlation;  genetic risk score;  genome-wide association study;  genotype phenotype correlation;  heritability;  hippocampus;  human;  human relation;  insomnia;  major clinical study;  major depression;  male;  mental disease;  mental instability;  quantitative trait locus;  schizophrenia;  sleep quality;  sleep time;  synaptic transmission;  bipolar disorder;  case control study;  genetic predisposition;  genetics;  human chromosome;  human genome;  major histocompatibility complex;  meta analysis;  multifactorial inheritance;  phenotype;  risk factor, Bipolar Disorder;  Case-Control Studies;  Chromosomes, Human;  Genetic Predisposition to Disease;  Genome, Human;  Genome-Wide Association Study;  Humans;  Major Histocompatibility Complex;  Multifactorial Inheritance;  Phenotype;  Quantitative Trait Loci;  Risk Factors",
    abstract = "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. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc."
}