Browsing by Author "Vieta, Eduard"

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    Characterisation of age and polarity at onset in bipolar disorder
    (Cambridge University Press, 2021-12) Kalman, Janos L.; Olde Loohuis, Loes M.; Vreeker, Annabel; McQuillin, Andrew; Stahl, Eli A.; Ruderfer, Douglas; Grigoroiu-Serbanescu, Maria; Panagiotaropoulou, Georgia; Ripke, Stephan; Bigdeli, Tim B.; Stein, Frederike; Meller, Tina; Meinert, Susanne; Pelin, Helena; Streit, Fabian; Papiol, Sergi; Adams, Mark J.; Adolfsson, Rolf; Adorjan, Kristina; Agartz, Ingrid; Aminoff, Sofie R.; Anderson-Schmidt, Heike; Andreassen, Ole A.; Ardau, Raffaella; Aubry, Jean-Michel; Balaban, Ceylan; Bass, Nicholas; Baune, Bernhard T.; Bellivier, Frank; Benabarre, Antoni; Bengesser, Susanne; Berrettini, Wade H.; Boks, Marco P.; Bromet, Evelyn J.; Brosch, Katharina; Budde, Monika; Byerley, William; Cervantes, Pablo; Chillotti, Catina; Cichon, Sven; Clark, Scott R.; Comes, Ashley L.; Corvin, Aiden; Coryell, William; Craddock, Nick; Craig, David W.; Croarkin, Paul E.; Cruceanu, Cristiana; Czerski, Piotr M.; Dalkner, Nina; Dannlowski, Udo; Degenhardt, Franziska; Del Zompo, Maria; DePaulo, J. Raymond; Djurovic, Srdjan; Edenberg, Howard J.; Al Eissa, Mariam; Elvsåshagen, Torbjørn; Etain, Bruno; Fanous, Ayman H.; Fellendorf, Frederike; Fiorentino, Alessia; Forstner, Andreas J.; Frye, Mark A.; Fullerton, Janice M.; Gade, Katrin; Garnham, Julie; Gershon, Elliot; Gill, Michael; Goes, Fernando S.; Gordon-Smith, Katherine; Grof, Paul; Guzman-Parra, Jose; Hahn, Tim; Hasler, Roland; Heilbronner, Maria; Heilbronner, Urs; Jamain, Stephane; Jimenez, Esther; Jones, Ian; Jones, Lisa; Jonsson, Lina; Kahn, Rene S.; Kelsoe, John R.; Kennedy, James L.; Kircher, Tilo; Kirov, George; Kittel-Schneider, Sarah; Klöhn-Saghatolislam, Farah; Knowles, James A.; Kranz, Thorsten M.; Lagerberg, Trine Vik; Landen, Mikael; Lawson, William B.; Leboyer, Marion; Li, Qingqin S.; Maj, Mario; Malaspina, Dolores; Manchia, Mirko; Mayoral, Fermin; McElroy, Susan L.; McInnis, Melvin G.; McIntosh, Andrew M.; Medeiros, Helena; Melle, Ingrid; Milanova, Vihra; Mitchell, Philip B.; Monteleone, Palmiero; Monteleone, Alessio Maria; Nöthen, Markus M.; Novak, Tomas; Nurnberger, John I.; O'Brien, Niamh; O'Connell, Kevin S.; O'Donovan, Claire; O'Donovan, Michael C.; Opel, Nils; Ortiz, Abigail; Owen, Michael J.; Pålsson, Erik; Pato, Carlos; Pato, Michele T.; Pawlak, Joanna; Pfarr, Julia-Katharina; Pisanu, Claudia; Potash, James B.; Rapaport, Mark H.; Reich-Erkelenz, Daniela; Reif, Andreas; Reininghaus, Eva; Repple, Jonathan; Richard-Lepouriel, Hélène; Rietschel, Marcella; Ringwald, Kai; Roberts, Gloria; Rouleau, Guy; Schaupp, Sabrina; Scheftner, William A.; Schmitt, Simon; Schofield, Peter R.; Schubert, K. Oliver; Schulte, Eva C.; Schweizer, Barbara; Senner, Fanny; Severino, Giovanni; Sharp, Sally; Slaney, Claire; Smeland, Olav B.; Sobell, Janet L.; Squassina, Alessio; Stopkova, Pavla; Strauss, John; Tortorella, Alfonso; Turecki, Gustavo; Twarowska-Hauser, Joanna; Veldic, Marin; Vieta, Eduard; Vincent, John B.; Xu, Wei; Zai, Clement C.; Zandi, Peter P.; Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group; International Consortium on Lithium Genetics (ConLiGen); Colombia-US Cross Disorder Collaboration in Psychiatric Genetics; Di Florio, Arianna; Smoller, Jordan W.; Biernacka, Joanna M.; McMahon, Francis J.; Alda, Martin; Müller-Myhsok, Bertram; Koutsouleris, Nikolaos; Falkai, Peter; Freimer, Nelson B.; Andlauer, Till F.M.; Schulze, Thomas G.; Ophoff, Roel A.; Biochemistry and Molecular Biology, School of Medicine
    Background: Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims: To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method: Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results: Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = -0.34 years, s.e. = 0.08), major depression (β = -0.34 years, s.e. = 0.08), schizophrenia (β = -0.39 years, s.e. = 0.08), and educational attainment (β = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions: AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
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    Fine-mapping genomic loci refines bipolar disorder risk genes
    (medRxiv, 2024-02-13) Koromina, Maria; Ravi, Ashvin; Panagiotaropoulou, Georgia; Schilder, Brian M.; Humphrey, Jack; Braun, Alice; Bidgeli, Tim; Chatzinakos, Chris; Coombes, Brandon; Kim, Jaeyoung; Liu, Xiaoxi; Terao, Chikashi; O'Connell, Kevin S.; Adams, Mark; Adolfsson, Rolf; Alda, Martin; Alfredsson, Lars; Andlauer, Till F. M.; Andreassen, Ole A.; Antoniou, Anastasia; Baune, Bernhard T.; Bengesser, Susanne; Biernacka, Joanna; Boehnke, Michael; Bosch, Rosa; Cairns, Murray; Carr, Vaughan J.; Casas, Miquel; Catts, Stanley; Cichon, Sven; Corvin, Aiden; Craddock, Nicholas; Dafnas, Konstantinos; Dalkner, Nina; Dannlowski, Udo; Degenhardt, Franziska; Di Florio, Arianna; Dikeos, Dimitris; Fellendorf, Frederike Tabea; Ferentinos, Panagiotis; Forstner, Andreas J.; Forty, Liz; Frye, Mark; Fullerton, Janice M.; Gawlik, Micha; Gizer, Ian R.; Gordon-Smith, Katherine; Green, Melissa J.; Grigoroiu-Serbanescu, Maria; Guzman-Parra, José; Hahn, Tim; Henskens, Frans; Hillert, Jan; Jablensky, Assen V.; Jones, Lisa; Jones, Ian; Jonsson, Lina; Kelsoe, John R.; Kircher, Tilo; Kirov, George; Kittel-Schneider, Sarah; Kogevinas, Manolis; Landén, Mikael; Leboyer, Marion; Lenger, Melanie; Lissowska, Jolanta; Lochner, Christine; Loughland, Carmel; MacIntyre, Donald; Martin, Nicholas G.; Maratou, Eirini; Mathews, Carol A.; Mayoral, Fermin; McElroy, Susan L.; McGregor, Nathaniel W.; McIntosh, Andrew; McQuillin, Andrew; Michie, Patricia; Milanova, Vihra; Mitchell, Philip B.; Moutsatsou, Paraskevi; Mowry, Bryan; Müller-Myhsok, Bertram; Myers, Richard; Nenadić, Igor; Nöthen, Markus M.; O'Donovan, Claire; O'Donovan, Michael; Ophoff, Roel A.; Owen, Michael J.; Pantelis, Chris; Pato, Carlos; Pato, Michele T.; Patrinos, George P.; Pawlak, Joanna M.; Perlis, Roy H.; Porichi, Evgenia; Posthuma, Danielle; Ramos-Quiroga, Josep Antoni; Reif, Andreas; Reininghaus, Eva Z.; Ribasés, Marta; Rietschel, Marcella; Schall, Ulrich; Schulze, Thomas G.; Scott, Laura; Scott, Rodney J.; Serretti, Alessandro; Shannon Weickert, Cynthia; Smoller, Jordan W.; Soler Artigas, Maria; Stein, Dan J.; Streit, Fabian; Toma, Claudio; Tooney, Paul; Vieta, Eduard; Vincent, John B.; Waldman, Irwin D.; Weickert, Thomas; Witt, Stephanie H.; Hong, Kyung Sue; Ikeda, Masashi; Iwata, Nakao; Świątkowska, Beata; Won, Hong-Hee; Edenberg, Howard J.; Ripke, Stephan; Raj, Towfique; Coleman, Jonathan R. I.; Mullins, Niamh; Biochemistry and Molecular Biology, School of Medicine
    Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).
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    Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
    (Springer Nature, 2021-06) Mullins, Niamh; Forstner, Andreas J.; O'Connell, Kevin S.; Coombes, Brandon; Coleman, Jonathan R.I.; Qiao, Zhen; Als, Thomas D.; Bigdeli, Tim B.; Børte, Sigrid; Bryois, Julien; Charney, Alexander W.; Drange, Ole Kristian; Gandal, Michael J.; Hagenaars, Saskia P.; Ikeda, Masashi; Kamitaki, Nolan; Kim, Minsoo; Krebs, Kristi; Panagiotaropoulou, Georgia; Schilder, Brian M.; Sloofman, Laura G.; Steinberg, Stacy; Trubetskoy, Vassily; Winsvold, Bendik S.; Won, Hong-Hee; Abramova, Liliya; Adorjan, Kristina; Agerbo, Esben; Al Eissa, Mariam; Albani, Diego; Alliey-Rodriguez, Ney; Anjorin, Adebayo; Antilla, Verneri; Antoniou, Anastasia; Awasthi, Swapnil; Baek, Ji Hyun; Bækvad-Hansen, Marie; Bass, Nicholas; Bauer, Michael; Beins, Eva C.; Bergen, Sarah E.; Birner, Armin; Pedersen, Carsten Bøcker; Bøen, Erlend; Boks, Marco P.; Bosch, Rosa; Brum, Murielle; Brumpton, Ben M.; Brunkhorst-Kanaan, Nathalie; Budde, Monika; Bybjerg-Grauholm, Jonas; Byerley, William; Cairns, Murray; Casas, Miquel; Cervantes, Pablo; Clarke, Toni-Kim; Cruceanu, Cristiana; Cuellar-Barboza, Alfredo; Cunningham, Julie; Curtis, David; Czerski, Piotr M.; Dale, Anders M.; Dalkner, Nina; David, Friederike S.; Degenhardt, Franziska; Djurovic, Srdjan; Dobbyn, Amanda L.; Douzenis, Athanassios; Elvsåshagen, Torbjørn; Escott-Price, Valentina; Ferrier, I. Nicol; Fiorentino, Alessia; Foroud, Tatiana M.; Forty, Liz; Frank, Josef; Frei, Oleksandr; Freimer, Nelson B.; Frisén, Louise; Gade, Katrin; Garnham, Julie; Gelernter, Joel; Pedersen, Marianne Giørtz; Gizer, Ian R.; Gordon, Scott D.; Gordon-Smith, Katherine; Greenwood, Tiffany A.; Grove, Jakob; Guzman-Parra, José; Ha, Kyooseob; Haraldsson, Magnus; Hautzinger, Martin; Heilbronner, Urs; Hellgren, Dennis; Herms, Stefan; Hoffmann, Per; Holmans, Peter A.; Huckins, Laura; Jamain, Stéphane; Johnson, Jessica S.; Kalman, Janos L.; Kamatani, Yoichiro; Kennedy, James L.; Kittel-Schneider, Sarah; Knowles, James A.; Kogevinas, Manolis; Koromina, Maria; Kranz, Thorsten M.; Kranzler, Henry R.; Kubo, Michiaki; Kupka, Ralph; Kushner, Steven A.; Lavebratt, Catharina; Lawrence, Jacob; Leber, Markus; Lee, Heon-Jeong; Lee, Phil H.; Levy, Shawn E.; Lewis, Catrin; Liao, Calwing; Lucae, Susanne; Lundberg, Martin; MacIntyre, Donald J.; Magnusson, Sigurdur H.; Maier, Wolfgang; Maihofer, Adam; Malaspina, Dolores; Maratou, Eirini; Martinsson, Lina; Mattheisen, Manuel; McCarroll, Steven A.; McGregor, Nathaniel W.; McGuffin, Peter; McKay, James D.; Medeiros, Helena; Medland, Sarah E.; Millischer, Vincent; Montgomery, Grant W.; Moran, Jennifer L.; Morris, Derek W.; Mühleisen, Thomas W.; O'Brien, Niamh; O'Donovan, Claire; Loohuis, Loes M. Olde; Oruc, Lilijana; Papiol, Sergi; Pardiñas, Antonio F.; Perry, Amy; Pfennig, Andrea; Porichi, Evgenia; Potash, James B.; Quested, Digby; Raj, Towfique; Rapaport, Mark H.; DePaulo, J. Raymond; Regeer, Eline J.; Rice, John P.; Rivas, Fabio; Rivera, Margarita; Roth, Julian; Roussos, Panos; Ruderfer, Douglas M.; Sánchez-Mora, Cristina; Schulte, Eva C.; Senner, Fanny; Sharp, Sally; Shilling, Paul D.; Sigurdsson, Engilbert; Sirignano, Lea; Slaney, Claire; Smeland, Olav B.; Smith, Daniel J.; Sobell, Janet L.; Søholm Hansen, Christine; Artigas, Maria Soler; Spijker, Anne T.; Stein, Dan J.; Strauss, John S.; Świątkowska, Beata; Terao, Chikashi; Thorgeirsson, Thorgeir E.; Toma, Claudio; Tooney, Paul; Tsermpini, Evangelia-Eirini; Vawter, Marquis P.; Vedder, Helmut; Walters, James T.R.; Witt, Stephanie H.; Xi, Simon; Xu, Wei; Yang, Jessica Mei Kay; Young, Allan H.; Young, Hannah; Zandi, Peter P.; Zhou, Hang; Zillich, Lea; Adolfsson, Rolf; Agartz, Ingrid; Alda, Martin; Alfredsson, Lars; Babadjanova, Gulja; Backlund, Lena; Baune, Bernhard T.; Bellivier, Frank; Bengesser, Susanne; Berrettini, Wade H.; Blackwood, Douglas H.R.; Boehnke, Michael; Børglum, Anders D.; Breen, Gerome; Carr, Vaughan J.; Catts, Stanley; Corvin, Aiden; Craddock, Nicholas; Dannlowski, Udo; Dikeos, Dimitris; Esko, Tõnu; Etain, Bruno; Ferentinos, Panagiotis; Frye, Mark; Fullerton, Janice M.; Gawlik, Micha; Gershon, Elliot S.; Goes, Fernando S.; Green, Melissa J.; Grigoroiu-Serbanescu, Maria; Hauser, Joanna; Henskens, Frans; Hillert, Jan; Hong, Kyung Sue; Hougaard, David M.; Hultman, Christina M.; Hveem, Kristian; Iwata, Nakao; Jablensky, Assen V.; Jones, Ian; Jones, Lisa A.; Kahn, René S.; Kelsoe, John R.; Kirov, George; Landén, Mikael; Leboyer, Marion; Lewis, Cathryn M.; Li, Qingqin S.; Lissowska, Jolanta; Lochner, Christine; Loughland, Carmel; Martin, Nicholas G.; Mathews, Carol A.; Mayoral, Fermin; McElroy, Susan L.; McIntosh, Andrew M.; McMahon, Francis J.; Melle, Ingrid; Michie, Patricia; Milani, Lili; Mitchell, Philip B.; Morken, Gunnar; Mors, Ole; Mortensen, Preben Bo; Mowry, Bryan; Müller-Myhsok, Bertram; Myers, Richard M.; Neale, Benjamin M.; Nievergelt, Caroline M.; Nordentoft, Merete; Nöthen, Markus M.; O'Donovan, Michael C.; Oedegaard, Ketil J.; Olsson, Tomas; Owen, Michael J.; Paciga, Sara A.; Pantelis, Chris; Pato, Carlos; Pato, Michele T.; Patrinos, George P.; Perlis, Roy H.; Posthuma, Danielle; Ramos-Quiroga, Josep Antoni; Reif, Andreas; Reininghaus, Eva Z.; Ribasés, Marta; Rietschel, Marcella; Ripke, Stephan; Rouleau, Guy A.; Saito, Takeo; Schall, Ulrich; Schalling, Martin; Schofield, Peter R.; Schulze, Thomas G.; Scott, Laura J.; Scott, Rodney J.; Serretti, Alessandro; Weickert, Cynthia Shannon; Smoller, Jordan W.; Stefansson, Hreinn; Stefansson, Kari; Stordal, Eystein; Streit, Fabian; Sullivan, Patrick F.; Turecki, Gustavo; Vaaler, Arne E.; Vieta, Eduard; Vincent, John B.; Waldman, Irwin D.; Weickert, Thomas W.; Werge, Thomas; Wray, Naomi R.; Zwart, John-Anker; Biernacka, Joanna M.; Nurnberger, John I.; Cichon, Sven; Edenberg, Howard J.; Stahl, Eli A.; McQuillin, Andrew; Florio, Arianna Di; Ophoff, Roel A.; Andreassen, Ole A.; Medical and Molecular Genetics, School of Medicine
    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.
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    Strategies and foundations for scientific discovery in longitudinal studies of bipolar disorder
    (Wiley, 2022) McInnis, Melvin G.; Andreassen, Ole A.; Andreazza, Ana C.; Alon, Uri; Berk, Michael; Brister, Teri; Burdick, Katherine E.; Cui, Donghong; Frye, Mark; Leboyer, Marion; Mitchell, Philip B.; Merikangas, Kathleen; Nierenberg, Andrew A.; Nurnberger, John I.; Pham, Daniel; Vieta, Eduard; Yatham, Lakshmi N.; Young, Allan H.; Psychiatry, School of Medicine
    Bipolar disorder (BD) is a complex and dynamic condition with a typical onset in late adolescence or early adulthood followed by an episodic course with intervening periods of subthreshold symptoms or euthymia. It is complicated by the accumulation of comorbid medical and psychiatric disorders. The etiology of BD remains unknown and no reliable biological markers have yet been identified. This is likely due to lack of comprehensive ontological framework and, most importantly, the fact that most studies have been based on small nonrepresentative clinical samples with cross‐sectional designs. We propose to establish large, global longitudinal cohorts of BD studied consistently in a multidimensional and multidisciplinary manner to determine etiology and help improve treatment. Herein we propose collection of a broad range of data that reflect the heterogenic phenotypic manifestations of BD that include dimensional and categorical measures of mood, neurocognitive, personality, behavior, sleep and circadian, life‐story, and outcomes domains. In combination with genetic and biological information such an approach promotes the integrating and harmonizing of data within and across current ontology systems while supporting a paradigm shift that will facilitate discovery and become the basis for novel hypotheses.