Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3076242 72 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Έτος δημοσίευσης:
2021
Συγγραφείς:
Mullins, N.
Forstner, A.J.
O’Connell, K.S.
Coombes, B.
Coleman, J.R.I.
Qiao, Z.
Als, T.D.
Bigdeli, T.B.
Børte, S.
Bryois, J.
Charney, A.W.
Drange, O.K.
Gandal, M.J.
Hagenaars, S.P.
Ikeda, M.
Kamitaki, N.
Kim, M.
Krebs, K.
Panagiotaropoulou, G.
Schilder, B.M.
Sloofman, L.G.
Steinberg, S.
Trubetskoy, V.
Winsvold, B.S.
Won, H.-H.
Abramova, L.
Adorjan, K.
Agerbo, E.
Al Eissa, M.
Albani, D.
Alliey-Rodriguez, N.
Anjorin, A.
Antilla, V.
Antoniou, A.
Awasthi, S.
Baek, J.H.
Bækvad-Hansen, M.
Bass, N.
Bauer, M.
Beins, E.C.
Bergen, S.E.
Birner, A.
Bøcker Pedersen, C.
Bøen, E.
Boks, M.P.
Bosch, R.
Brum, M.
Brumpton, B.M.
Brunkhorst-Kanaan, N.
Budde, M.
Bybjerg-Grauholm, J.
Byerley, W.
Cairns, M.
Casas, M.
Cervantes, P.
Clarke, T.-K.
Cruceanu, C.
Cuellar-Barboza, A.
Cunningham, J.
Curtis, D.
Czerski, P.M.
Dale, A.M.
Dalkner, N.
David, F.S.
Degenhardt, F.
Djurovic, S.
Dobbyn, A.L.
Douzenis, A.
Elvsåshagen, T.
Escott-Price, V.
Ferrier, I.N.
Fiorentino, A.
Foroud, T.M.
Forty, L.
Frank, J.
Frei, O.
Freimer, N.B.
Frisén, L.
Gade, K.
Garnham, J.
Gelernter, J.
Giørtz Pedersen, M.
Gizer, I.R.
Gordon, S.D.
Gordon-Smith, K.
Greenwood, T.A.
Grove, J.
Guzman-Parra, J.
Ha, K.
Haraldsson, M.
Hautzinger, M.
Heilbronner, U.
Hellgren, D.
Herms, S.
Hoffmann, P.
Holmans, P.A.
Huckins, L.
Jamain, S.
Johnson, J.S.
Kalman, J.L.
Kamatani, Y.
Kennedy, J.L.
Kittel-Schneider, S.
Knowles, J.A.
Kogevinas, M.
Koromina, M.
Kranz, T.M.
Kranzler, H.R.
Kubo, M.
Kupka, R.
Kushner, S.A.
Lavebratt, C.
Lawrence, J.
Leber, M.
Lee, H.-J.
Lee, P.H.
Levy, S.E.
Lewis, C.
Liao, C.
Lucae, S.
Lundberg, M.
MacIntyre, D.J.
Magnusson, S.H.
Maier, W.
Maihofer, A.
Malaspina, D.
Maratou, E.
Martinsson, L.
Mattheisen, M.
McCarroll, S.A.
McGregor, N.W.
McGuffin, P.
McKay, J.D.
Medeiros, H.
Medland, S.E.
Millischer, V.
Montgomery, G.W.
Moran, J.L.
Morris, D.W.
Mühleisen, T.W.
O’Brien, N.
O’Donovan, C.
Olde Loohuis, L.M.
Oruc, L.
Papiol, S.
Pardiñas, A.F.
Perry, A.
Pfennig, A.
Porichi, E.
Potash, J.B.
Quested, D.
Raj, T.
Rapaport, M.H.
DePaulo, J.R.
Regeer, E.J.
Rice, J.P.
Rivas, F.
Rivera, M.
Roth, J.
Roussos, P.
Ruderfer, D.M.
Sánchez-Mora, C.
Schulte, E.C.
Senner, F.
Sharp, S.
Shilling, P.D.
Sigurdsson, E.
Sirignano, L.
Slaney, C.
Smeland, O.B.
Smith, D.J.
Sobell, J.L.
Søholm Hansen, C.
Soler Artigas, M.
Spijker, A.T.
Stein, D.J.
Strauss, J.S.
Świątkowska, B.
Terao, C.
Thorgeirsson, T.E.
Toma, C.
Tooney, P.
Tsermpini, E.-E.
Vawter, M.P.
Vedder, H.
Walters, J.T.R.
Witt, S.H.
Xi, S.
Xu, W.
Yang, J.M.K.
Young, A.H.
Young, H.
Zandi, P.P.
Zhou, H.
Zillich, L.
Adolfsson, R.
Agartz, I.
Alda, M.
Alfredsson, L.
Babadjanova, G.
Backlund, L.
Baune, B.T.
Bellivier, F.
Bengesser, S.
Berrettini, W.H.
Blackwood, D.H.R.
Boehnke, M.
Børglum, A.D.
Breen, G.
Carr, V.J.
Catts, S.
Corvin, A.
Craddock, N.
Dannlowski, U.
Dikeos, D.
Esko, T.
Etain, B.
Ferentinos, P.
Frye, M.
Fullerton, J.M.
Gawlik, M.
Gershon, E.S.
Goes, F.S.
Green, M.J.
Grigoroiu-Serbanescu, M.
Hauser, J.
Henskens, F.
Hillert, J.
Hong, K.S.
Hougaard, D.M.
Hultman, C.M.
Hveem, K.
Iwata, N.
Jablensky, A.V.
Jones, I.
Jones, L.A.
Kahn, R.S.
Kelsoe, J.R.
Kirov, G.
Landén, M.
Leboyer, M.
Lewis, C.M.
Li, Q.S.
Lissowska, J.
Lochner, C.
Loughland, C.
Martin, N.G.
Mathews, C.A.
Mayoral, F.
McElroy, S.L.
McIntosh, A.M.
McMahon, F.J.
Melle, I.
Michie, P.
Milani, L.
Mitchell, P.B.
Morken, G.
Mors, O.
Mortensen, P.B.
Mowry, B.
Müller-Myhsok, B.
Myers, R.M.
Neale, B.M.
Nievergelt, C.M.
Nordentoft, M.
Nöthen, M.M.
O’Donovan, M.C.
Oedegaard, K.J.
Olsson, T.
Owen, M.J.
Paciga, S.A.
Pantelis, C.
Pato, C.
Pato, M.T.
Patrinos, G.P.
Perlis, R.H.
Posthuma, D.
Ramos-Quiroga, J.A.
Reif, A.
Reininghaus, E.Z.
Ribasés, M.
Rietschel, M.
Ripke, S.
Rouleau, G.A.
Saito, T.
Schall, U.
Schalling, M.
Schofield, P.R.
Schulze, T.G.
Scott, L.J.
Scott, R.J.
Serretti, A.
Shannon Weickert, C.
Smoller, J.W.
Stefansson, H.
Stefansson, K.
Stordal, E.
Streit, F.
Sullivan, P.F.
Turecki, G.
Vaaler, A.E.
Vieta, E.
Vincent, J.B.
Waldman, I.D.
Weickert, T.W.
Werge, T.
Wray, N.R.
Zwart, J.-A.
Biernacka, J.M.
Nurnberger, J.I.
Cichon, S.
Edenberg, H.J.
Stahl, E.A.
McQuillin, A.
Di Florio, A.
Ophoff, R.A.
Andreassen, O.A.
HUNT All-In Psychiatry
Περιοδικό:
Nature Genetics
Εκδότης:
Lithuanian Nature Research Centre
Τόμος:
53
Αριθμός / τεύχος:
6
Σελίδες:
817-829
Λέξεις-κλειδιά:
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
Επίσημο URL (Εκδότης):
DOI:
10.1038/s41588-021-00857-4
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