Citations 2
Genomic dimensions deconstruct the clinical heterogeneity of bipolar disorder
Veen, Tracey van der , Tesfaye, Markos , Yang, Jessica , Boltz, Toni , David, Friederike S. , Crinion, Shane , Koromina, Maria , Bigdeli, Tim B., Coombes, Brandon J., Panagiotaropoulou, Georgia, Parker, Nadine, Sung, Heejong , Bass, Nicholas, Coleman, Jonathan R. I., Guzman-Parra, José , Kálmán, János , McGrouther, Caroline C., Rangan, Aaditya V. , Scott, Katie , Vreeker, Annabel , Bauer, Michael , Brunkhorst-Kanaan, Nathalie, Byerley, William , Cervantes, Pablo , Chatzinakos, Chris , Claus, Isabelle , Cruceanu, Cristiana , Cuellar-Barboza, Alfredo, Dafnas, Konstantinos , Degenhardt, Franziska, Fanous, Ayman H. , Ferrier, I. 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No container title available | June 25, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
ABSTRACT Bipolar disorder’s (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder—and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic–GABAergic gradient along the psychotic factor. BD’s genetic architecture appears hierarchical—a general liability resolving into dimensions of course and comorbidity beyond diagnostic subtypes.
The Role of Variation at AβPP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease
Gerrish, Amy , Russo, Giancarlo , Richards, Alexander , Moskvina, Valentina, Ivanov, Dobril , Harold, Denise , Sims, Rebecca , Abraham, Richard, Hollingworth, Paul, Chapman, Jade , Hamshere, Marian L. , Pahwa, Jaspreet Singh, Dowzell, Kimberley, Jones, Nicola, Thomas, Charlene , Stretton, Alexandra, Morgan, Angharad R., Lovestone, Simon , Powell, John , Proitsi, Petroula , Brayne, Carol , Gill, Michael , Lynch, Aoibhinn, Morgan, Kevin , Brown, Kristelle, Passmore, Peter , Craig, David W. , McGuinness, Bernadette , Todd, Stephen , Johnston, Janet, Smith, A. David , Love, Seth , Kehoe, Patrick G. , Hardy, John , Mead, Simon , Fox, Nick C. , Rossor, Martin N. , Collinge, John, Maier, Wolfgang, Jessen, Frank , Kölsch, Heike, Schürmann, Britta, Bussche, Hendrik van den, Heuser, Isabella , Kornhuber, Johannes , Wiltfang, Jens , Dichgans, Martin , Frölich, Lutz, Hampel, Harald , Hüll, Michael, Goate, Alison , Kauwe, John, Cruchaga, Carlos , Nowotny, Petra, Morris, John C. , Mayo, Kevin H. , Livingston, Gill , Gurling, Hugh, McQuillin, Andrew , Gwilliam, Rhian, Deloukas, Panagiotis, Davies, Gail , Starr, John M. , Deary, Ian J. , Al‐Chalabi, Ammar , Shaw, Christopher E. , Tsolaki, Magda , Singleton, Andrew B., Guerreiro, Rita , Mühleisen, Thomas W. , Nöthen, Markus M. , Moebus, Susanne , Jöckel, Karl‐Heinz , Klopp, Norman, Wichmann, H‐Erich, Carrasquillo, Minerva M., Younkin, Steven G., Jones, Lesley , Holmans, Peter , O‘Donovan, Michael , Williams, Julie , Deloukas, Panos , Escott‐Price, Valentina , Denning, Nicola , Dichgans, Martin , Cruchaga, Carlos , Kornhuber, Johannes , Nöthen, Markus M , Hardy, John , Moebus, Susanne , Williams, Amy L. , Lupton, Michelle K. , Rubinsztein, David Chaim , LAWLOR, BRIAN A. , Holmes, Clive , Mann, David , Heun, Reinhard , Rujescu, Dan , Bass, Nicholas , Harris, Sarah , Carrasquillo, Minerva M. , Pankratz, V. Shane , Owen, Michael J. , Fox, Nick C , Morris, John C , Wiltfang, Jens , Al-Chalabi, Ammar , Tsolaki, Magda , Goate, Alison M , McQuillin, Andrew , Escott-Price, Valentina
Journal of Alzheimer's Disease | May 16, 2018 | Volume: 28 | Issue: 2 | Pages: 377-387