Analysis of shared heritability in common disorders of the brain

• Published in: Science (American Association for the Advancement of Science) Vol. 360; no. 6395; p. 1313
• Main Authors: Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K, Walters, Raymond K, Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J, Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A, Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H, Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-François, Duron, Emmanuelle, Vardarajan, Badri N, Reitz, Christiane, Goate, Alison M, Huentelman, Matthew J, Kamboh, M Ilyas, Larson, Eric B, Rogaeva, Ekaterina, St George-Hyslop, Peter, Hakonarson, Hakon, Kukull, Walter A, Farrer, Lindsay A, Barnes, Lisa L, Beach, Thomas G, Demirci, F Yesim, Head, Elizabeth, Hulette, Christine M, Jicha, Gregory A, Kauwe, John S K, Kaye, Jeffrey A, Leverenz, James B, Levey, Allan I, Lieberman, Andrew P, Pankratz, Vernon S, Poon, Wayne W, Quinn, Joseph F, Saykin, Andrew J, Schneider, Lon S, Smith, Amanda G, Sonnen, Joshua A, Stern, Robert A, Van Deerlin, Vivianna M, Van Eldik, Linda J, Harold, Denise, Russo, Giancarlo, Rubinsztein, David C, Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C, Hampel, Harald, Owen, Michael J, Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M, Rossor, Martin, Lupton, Michelle K, Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C, Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, van der Lee, Sven J, De Jager, Philip L, Geschwind, Daniel H, Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I, Ransmayr, Gerhard, Hyman, Bradley T, Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nicholas, Kurth, Tobias
• Format: Journal Article Web Resource
• Language: English
• Published: United States The American Association for the Advancement of Science 22.06.2018; American Association for the Advancement of Science (AAAS); American Association for the Advancement of Science
• Subjects: Activity patterns; Alzheimer's disease; Anorexia; Attention deficit hyperactivity disorder; Behavior Change; Behavior disorders; Biological effects; Bipolar disorder; Brain; Brain Diseases; Brain Diseases - classification; Brain Diseases - diagnosis; Brain Diseases - genetics; Classification; Cognitive ability; Comorbidity; Consortia; Correlation; Correlation analysis; Crohn's Disease; Diagnostic systems; Disorders; Eating disorders; Epidemiology; Etiology; Genetic diversity; Genetic Variation; Genetics; Genetics & genetic processes; Genome-Wide Association Study; Genomes; Gilles de la Tourette syndrome; Génétique & processus génétiques; Headache; Heritability; Heterogeneity; Human health and pathology; Humans; Ischemia; Life Sciences; Medicin och hälsovetenskap; Mental depression; Mental Disorders; Mental Disorders - classification; Mental Disorders - diagnosis; Mental Disorders - genetics; Migraine; Neurodegenerative diseases; Neurological diseases; Neurological disorders; Neurons and Cognition; Patients; Personality; Personality Measures; Personality Traits; Phenotype; Phenotypes; Population (statistical); Post traumatic stress disorder; Posttraumatic Stress Disorder; Proteins; Psychiatry; Psychological Characteristics; Quantitative Trait, Heritable; Risk analysis; Risk assessment; Risk Factors; Risk sharing; Scaffolding; Schizophrenia; Sciences du vivant; Statistics
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aap8757

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.