Analysis of shared heritability in common disorders of the brain

Brainstorm Consortium; Verneri Anttila; Brendan Bulik-Sullivan; Hilary K Finucane; Raymond K Walters; Jose Bras; Laramie Duncan; Valentina Escott-Price; Guido J Falcone; Padhraig Gormley; Rainer Malik; Nikolaos A Patsopoulos; Stephan Ripke; Zhi Wei; Dongmei Yu; Phil H Lee; Patrick Turley; Benjamin Grenier-Boley; Vincent Chouraki; Yoichiro Kamatani; Claudine Berr; Luc Letenneur; Didier Hannequin; Philippe Amouyel; Anne Boland; Jean-François Deleuze; Emmanuelle Duron; Badri N Vardarajan; Christiane Reitz; Alison M Goate; Matthew J Huentelman; M Ilyas Kamboh; Eric B Larson; Ekaterina Rogaeva; Peter St George-Hyslop; Hakon Hakonarson; Walter A Kukull; Lindsay A Farrer; Lisa L Barnes; Thomas G Beach; F Yesim Demirci; Elizabeth Head; Christine M Hulette; Gregory A Jicha; John S K Kauwe; Jeffrey A Kaye; Amanda G Smith; Keith Matthews; Andrew McIntosh; Mary M Robertson; David Cohen

doi:10.1126/science.aap8757

Analysis of shared heritability in common disorders of the brain

Brainstorm Consortium, Verneri Anttila, Brendan Bulik-Sullivan, Hilary K Finucane, Raymond K Walters, Jose Bras, Laramie Duncan, Valentina Escott-Price, Guido J Falcone, Padhraig Gormley, Rainer Malik, Nikolaos A Patsopoulos, Stephan Ripke, Zhi Wei, Dongmei Yu, Phil H Lee, Patrick Turley, Benjamin Grenier-Boley, Vincent Chouraki, Yoichiro KamataniClaudine Berr, Luc Letenneur, Didier Hannequin, Philippe Amouyel, Anne Boland, Jean-François Deleuze, Emmanuelle Duron, Badri N Vardarajan, Christiane Reitz, Alison M Goate, Matthew J Huentelman, M Ilyas Kamboh, Eric B Larson, Ekaterina Rogaeva, Peter St George-Hyslop, Hakon Hakonarson, Walter A Kukull, Lindsay A Farrer, Lisa L Barnes, Thomas G Beach, F Yesim Demirci, Elizabeth Head, Christine M Hulette, Gregory A Jicha, John S K Kauwe, Jeffrey A Kaye, Amanda G Smith, Keith Matthews, Andrew McIntosh, Mary M Robertson, David Cohen

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Abstract

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.

Original language	English
Article number	eaap8757
Pages (from-to)	1-15
Number of pages	15
Journal	Science
Volume	360
Issue number	6395
DOIs	https://doi.org/10.1126/science.aap8757
Publication status	Published - 22 Jun 2018

Keywords

Brain Diseases/classification
Genetic Variation
Genome-Wide Association Study
Humans
Mental Disorders/classification
Phenotype
Quantitative Trait, Heritable
Risk Factors

ASJC Scopus subject areas

General

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Author Accepted ManuscriptAccepted author manuscript, 1.29 MB
Author Accepted Manuscript: Supplemental MaterialAccepted author manuscript, 5.7 MB

Cite this

Brainstorm Consortium, Anttila, V., Bulik-Sullivan, B., Finucane, H. K., Walters, R. K., Bras, J., Duncan, L., Escott-Price, V., Falcone, G. J., Gormley, P., Malik, R., Patsopoulos, N. A., Ripke, S., Wei, Z., Yu, D., Lee, P. H., Turley, P., Grenier-Boley, B., Chouraki, V., ... Cohen, D. (2018). Analysis of shared heritability in common disorders of the brain. Science, 360(6395), 1-15. Article eaap8757. https://doi.org/10.1126/science.aap8757

@article{2b0477abe32b4fdea560e2a07616429b,

title = "Analysis of shared heritability in common disorders of the brain",

abstract = "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.",

keywords = "Brain Diseases/classification, Genetic Variation, Genome-Wide Association Study, Humans, Mental Disorders/classification, Phenotype, Quantitative Trait, Heritable, Risk Factors",

author = "{Brainstorm Consortium} and Verneri Anttila and Brendan Bulik-Sullivan and Finucane, {Hilary K} and Walters, {Raymond K} and Jose Bras and Laramie Duncan and Valentina Escott-Price and Falcone, {Guido J} and Padhraig Gormley and Rainer Malik and Patsopoulos, {Nikolaos A} and Stephan Ripke and Zhi Wei and Dongmei Yu and Lee, {Phil H} and Patrick Turley and Benjamin Grenier-Boley and Vincent Chouraki and Yoichiro Kamatani and Claudine Berr and Luc Letenneur and Didier Hannequin and Philippe Amouyel and Anne Boland and Jean-Fran{\c c}ois Deleuze and Emmanuelle Duron and Vardarajan, {Badri N} and Christiane Reitz and Goate, {Alison M} and Huentelman, {Matthew J} and Kamboh, {M Ilyas} and Larson, {Eric B} and Ekaterina Rogaeva and {St George-Hyslop}, Peter and Hakon Hakonarson and Kukull, {Walter A} and Farrer, {Lindsay A} and Barnes, {Lisa L} and Beach, {Thomas G} and Demirci, {F Yesim} and Elizabeth Head and Hulette, {Christine M} and Jicha, {Gregory A} and Kauwe, {John S K} and Kaye, {Jeffrey A} and Smith, {Amanda G} and Keith Matthews and Andrew McIntosh and Robertson, {Mary M} and David Cohen",

note = "Copyright {\textcopyright} 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2018",

month = jun,

day = "22",

doi = "10.1126/science.aap8757",

language = "English",

volume = "360",

pages = "1--15",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6395",

}

Brainstorm Consortium, Anttila, V, Bulik-Sullivan, B, Finucane, HK, Walters, RK, Bras, J, Duncan, L, Escott-Price, V, Falcone, GJ, Gormley, P, Malik, R, Patsopoulos, NA, Ripke, S, Wei, Z, Yu, D, Lee, PH, Turley, P, Grenier-Boley, B, Chouraki, V, Kamatani, Y, Berr, C, Letenneur, L, Hannequin, D, Amouyel, P, Boland, A, Deleuze, J-F, Duron, E, Vardarajan, BN, Reitz, C, Goate, AM, Huentelman, MJ, Kamboh, MI, Larson, EB, Rogaeva, E, St George-Hyslop, P, Hakonarson, H, Kukull, WA, Farrer, LA, Barnes, LL, Beach, TG, Demirci, FY, Head, E, Hulette, CM, Jicha, GA, Kauwe, JSK, Kaye, JA, Smith, AG, Matthews, K, McIntosh, A, Robertson, MM & Cohen, D 2018, 'Analysis of shared heritability in common disorders of the brain', Science, vol. 360, no. 6395, eaap8757, pp. 1-15. https://doi.org/10.1126/science.aap8757

TY - JOUR

T1 - Analysis of shared heritability in common disorders of the brain

AU - Brainstorm Consortium

AU - Anttila, Verneri

AU - Bulik-Sullivan, Brendan

AU - Finucane, Hilary K

AU - Walters, Raymond K

AU - Bras, Jose

AU - Duncan, Laramie

AU - Escott-Price, Valentina

AU - Falcone, Guido J

AU - Gormley, Padhraig

AU - Malik, Rainer

AU - Patsopoulos, Nikolaos A

AU - Ripke, Stephan

AU - Wei, Zhi

AU - Yu, Dongmei

AU - Lee, Phil H

AU - Turley, Patrick

AU - Grenier-Boley, Benjamin

AU - Chouraki, Vincent

AU - Kamatani, Yoichiro

AU - Berr, Claudine

AU - Letenneur, Luc

AU - Hannequin, Didier

AU - Amouyel, Philippe

AU - Boland, Anne

AU - Deleuze, Jean-François

AU - Duron, Emmanuelle

AU - Vardarajan, Badri N

AU - Reitz, Christiane

AU - Goate, Alison M

AU - Huentelman, Matthew J

AU - Kamboh, M Ilyas

AU - Larson, Eric B

AU - Rogaeva, Ekaterina

AU - St George-Hyslop, Peter

AU - Hakonarson, Hakon

AU - Kukull, Walter A

AU - Farrer, Lindsay A

AU - Barnes, Lisa L

AU - Beach, Thomas G

AU - Demirci, F Yesim

AU - Head, Elizabeth

AU - Hulette, Christine M

AU - Jicha, Gregory A

AU - Kauwe, John S K

AU - Kaye, Jeffrey A

AU - Smith, Amanda G

AU - Matthews, Keith

AU - McIntosh, Andrew

AU - Robertson, Mary M

AU - Cohen, David

PY - 2018/6/22

Y1 - 2018/6/22

N2 - 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.

AB - 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.

KW - Brain Diseases/classification

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - Humans

KW - Mental Disorders/classification

KW - Phenotype

KW - Quantitative Trait, Heritable

KW - Risk Factors

U2 - 10.1126/science.aap8757

DO - 10.1126/science.aap8757

M3 - Article

C2 - 29930110

SN - 0036-8075

VL - 360

SP - 1

EP - 15

JO - Science

JF - Science

IS - 6395

M1 - eaap8757

ER -

Analysis of shared heritability in common disorders of the brain

Abstract

Keywords

ASJC Scopus subject areas

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