Analysis of shared heritability in common disorders of the brain

Анализ общей наследуемости распространённых заболеваний головного мозга
Sudha Seshadri, Bradley T. Hyman, Allan I. Levey, Jerome I. Rotter, Daniel H. Geschwind, Joshua A. Sonnen, Ammar Al‐Chalabi, Håkon Håkonarson, Laramie E. Duncan, Dongmei Yu, Andrew McQuillin, Alison Goate, Lindsay A. Farrer, Peter Passmore, Michael J. Owen, Michelle K. Lupton, Kevin Morgan, John S.K. Kauwe, Carlos Cruchaga, José Brás, Benjamin Grenier‐Boley, F. Yesim Demirci, Ekaterina Rogaeva, M. Ilyas Kamboh, Peter St George‐Hyslop, Nick C. Fox, Martin N. Rossor, Denise Harold, Joshua C. Bis, Giancarlo Russo, Vincent Chouraki, Badri N. Vardarajan, Yoichiro Kamatani, Agustı́n Ruiz, Christiane Reitz, Claudine Berr, Luc Letenneur, David C. Rubinsztein, Matthew J. Huentelman, Antony Bayer, Magda Tsolaki, Petroula Proitsi, Harald Hampel, Simon Mead, Walter A. Kukull, Didier Hannequin, Markus J. Riemenschneider, Merçé Boada, Markus M. Nöthen, Philippe Amouyel, Sven J. van der Lee, Anne Boland, Per Hoffmann, Alexa Beiser, Steffi G. Riedel‐Heller, Johannes Kornhuber, Lisa L. Barnes, Christine M. Hulette, Jonathan Kaye, James B. Leverenz, Andrew P. Lieberman, V. Shane Pankratz, Wayne W. Poon, Joseph F. Quinn, Andrew J. Saykin, Lon S. Schneider, Robert A. Stern, Vivianna M. Van Deerlin, Linda J. Van Eldik, Valentina Escott‐Price, Jean‐François Deleuze, Eric B. Larson, Jonathan M. Schott, Stephan Ripke, Verneri Anttila, Guido J. Falcone, Zhi Wei, Kai-How Farh, Philip L. De Jager, Hilary K. Finucane, Gerhard Ransmayr, Nikolaos A. Patsopoulos, Bendik S. Winsvold, Raymond K. Walters, Priit Palta, Kenneth Rice, Elizabeth Head, Brendan Bulik‐Sullivan, Padhraig Gormley, Patrick Turley, Montserrat Alegret, Thomas G. Beach, Gregory A. Jicha, Rainer Malik, Phil H. Lee, Emmanuelle Duron, Amanda Smith, Brian Lawlor, Ester Cuenca-León, Nicholas A. Furlotte, Yoichiro Kamatani, Jeffrey A. Kaye, Anthony Bayer, Petra Proitsi, Joshua C Bis, Matthias Riemenschneider
2018-06-21

brain disordersdiagnostic misclassificationgenetic correlationsgenome-wide association studiesshared heritability
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.
1
Psychiatric disorders showed substantial common-variant risk sharing, whereas neurological disorders were genetically more distinct from one another and from psychiatric disorders.
2
Significant genetic sharing was identified between brain disorders and multiple brain-related phenotypes, including cognitive measures, across 1,191,588 individuals.
3
Simulations demonstrated that statistical power, diagnostic misclassification, and phenotypic heterogeneity can influence estimated genetic correlations.
4
The findings support common genetic variation as an important risk factor and heritability-based methods as useful tools for studying brain-disorder etiology.
5
The study quantified genetic sharing across 25 brain disorders using genome-wide association data from 265,218 patients and 784,643 controls.

Common brain disorders (25 disorders) and related brain phenotypes analyzed for genetic sharing using genome-wide association study data

Shared common-variant genetic risk and heritability-based relationships among brain disorders and phenotypes, including the effects of diagnostic misclassification and phenotypic heterogeneity

Publication Details
Publication Date
2018-06-21
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Authors
Sudha Seshadri
Bradley T. Hyman
Allan I. Levey
Jerome I. Rotter
Daniel H. Geschwind
Joshua A. Sonnen
Ammar Al‐Chalabi
Håkon Håkonarson
Laramie E. Duncan
Dongmei Yu
Andrew McQuillin
Alison Goate
Lindsay A. Farrer
Peter Passmore
Michael J. Owen
Michelle K. Lupton
Kevin Morgan
John S.K. Kauwe
Carlos Cruchaga
José Brás
Benjamin Grenier‐Boley
F. Yesim Demirci
Ekaterina Rogaeva
M. Ilyas Kamboh
Peter St George‐Hyslop
Nick C. Fox
Martin N. Rossor
Denise Harold
Joshua C. Bis
Giancarlo Russo
Vincent Chouraki
Badri N. Vardarajan
Yoichiro Kamatani
Agustı́n Ruiz
Christiane Reitz
Claudine Berr
Luc Letenneur
David C. Rubinsztein
Matthew J. Huentelman
Antony Bayer
Magda Tsolaki
Petroula Proitsi
Harald Hampel
Simon Mead
Walter A. Kukull
Didier Hannequin
Markus J. Riemenschneider
Merçé Boada
Markus M. Nöthen
Philippe Amouyel
Sven J. van der Lee
Anne Boland
Per Hoffmann
Alexa Beiser
Steffi G. Riedel‐Heller
Johannes Kornhuber
Lisa L. Barnes
Christine M. Hulette
Jonathan Kaye
James B. Leverenz
Andrew P. Lieberman
V. Shane Pankratz
Wayne W. Poon
Joseph F. Quinn
Andrew J. Saykin
Lon S. Schneider
Robert A. Stern
Vivianna M. Van Deerlin
Linda J. Van Eldik
Valentina Escott‐Price
Jean‐François Deleuze
Eric B. Larson
Jonathan M. Schott
Stephan Ripke
Verneri Anttila
Guido J. Falcone
Zhi Wei
Kai-How Farh
Philip L. De Jager
Hilary K. Finucane
Gerhard Ransmayr
Nikolaos A. Patsopoulos
Bendik S. Winsvold
Raymond K. Walters
Priit Palta
Kenneth Rice
Elizabeth Head
Brendan Bulik‐Sullivan
Padhraig Gormley
Patrick Turley
Montserrat Alegret
Thomas G. Beach
Gregory A. Jicha
Rainer Malik
Phil H. Lee
Emmanuelle Duron
Amanda Smith
Brian Lawlor
Ester Cuenca-León
Nicholas A. Furlotte
Yoichiro Kamatani
Jeffrey A. Kaye
Anthony Bayer
Petra Proitsi
Joshua C Bis
Matthias Riemenschneider
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