Browsing by Author "Cervantes, Pablo"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders
    (Elsevier, 2022) Blokland, Gabriëlla A. M.; Grove, Jakob; Chen, Chia-Yen; Cotsapas, Chris; Tobet, Stuart; Handa, Robert; Schizophrenia Working Group of the Psychiatric Genomics Consortium; St. Clair, David; Lencz, Todd; Mowry, Bryan J.; Periyasamy, Sathish; Cairns, Murray J.; Tooney, Paul A.; Wu, Jing Qin; Kelly, Brian; Kirov, George; Sullivan, Patrick F.; Corvin, Aiden; Riley, Brien P.; Esko, Tõnu; Milani, Lili; Jönsson, Erik G.; Palotie, Aarno; Ehrenreich, Hannelore; Begemann, Martin; Steixner-Kumar, Agnes; Sham, Pak C.; Iwata, Nakao; Weinberger, Daniel R.; Gejman, Pablo V.; Sanders, Alan R.; Buxbaum, Joseph D.; Rujescu, Dan; Giegling, Ina; Konte, Bettina; Hartmann, Annette M.; Bramon, Elvira; Murray, Robin M.; Pato, Michele T.; Lee, Jimmy; Melle, Ingrid; Molden, Espen; Ophoff, Roel A.; McQuillin, Andrew; Bass, Nicholas J.; Adolfsson, Rolf; Malhotra, Anil K.; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Martin, Nicholas G.; Fullerton, Janice M.; Mitchell, Philip B.; Schofield, Peter R.; Forstner, Andreas J.; Degenhardt, Franziska; Schaupp, Sabrina; Comes, Ashley L.; Kogevinas, Manolis; Guzman-Parra, José; Reif, Andreas; Streit, Fabian; Sirignano, Lea; Cichon, Sven; Grigoroiu-Serbanescu, Maria; Hauser, Joanna; Lissowska, Jolanta; Mayoral, Fermin; Müller-Myhsok, Bertram; Świątkowska, Beata; Schulze, Thomas G.; Nöthen, Markus M.; Rietschel, Marcella; Kelsoe, John; Leboyer, Marion; Jamain, Stéphane; Etain, Bruno; Bellivier, Frank; Vincent, John B.; Alda, Martin; O'Donovan, Claire; Cervantes, Pablo; Biernacka, Joanna M.; Frye, Mark; McElroy, Susan L.; Scott, Laura J.; Stahl, Eli A.; Landén, Mikael; Hamshere, Marian L.; Smeland, Olav B.; Djurovic, Srdjan; Vaaler, Arne E.; Andreassen, Ole A.; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Baune, Bernhard T.; Air, Tracy; Preisig, Martin; Uher, Rudolf; Levinson, Douglas F.; Weissman, Myrna M.; Potash, James B.; Shi, Jianxin; Knowles, James A.; Perlis, Roy H.; Lucae, Susanne; Boomsma, Dorret I.; Penninx, Brenda W. J. H.; Hottenga, Jouke-Jan; de Geus, Eco J. C.; Willemsen, Gonneke; Milaneschi, Yuri; Tiemeier, Henning; Grabe, Hans J.; Teumer, Alexander; Van der Auwera, Sandra; Völker, Uwe; Hamilton, Steven P.; Magnusson, Patrik K. E.; Viktorin, Alexander; Mehta, Divya; Mullins, Niamh; Adams, Mark J.; Breen, Gerome; McIntosh, Andrew M.; Lewis, Cathryn M.; Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium; iPSYCH; Hougaard, David M.; Nordentoft, Merete; Mors, Ole; Mortensen, Preben B.; Werge, Thomas; Als, Thomas D.; Børglum, Anders D.; Petryshen, Tracey L.; Smoller, Jordan W.; Goldstein, Jill M.; Psychiatry, School of Medicine
    Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10-8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10-6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10-7; rs73033497, p = 8.8 × 10-7; rs7914279, p = 6.4 × 10-7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10-7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10-7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10-7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.