Analysis of shared heritability in common disorders of the brain

, 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 & 31 others 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

Research output: Contribution to journalArticle

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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 languageEnglish
Article numbereaap8757
Pages (from-to)1-15
Number of pages15
JournalScience
Volume360
Issue number6395
DOIs
Publication statusPublished - 22 Jun 2018

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Brain Diseases
Psychiatry
Phenotype
Genetic Heterogeneity
Genome-Wide Association Study
Nervous System Diseases
Comorbidity
Brain

Keywords

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

Cite this

, Anttila, V., Bulik-Sullivan, B., Finucane, H. K., Walters, R. K., Bras, J., ... Cohen, D. (2018). Analysis of shared heritability in common disorders of the brain. Science, 360(6395), 1-15. [eaap8757]. https://doi.org/10.1126/science.aap8757
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 ; Smith, Amanda G ; Matthews, Keith ; McIntosh, Andrew ; Robertson, Mary M ; Cohen, David. / Analysis of shared heritability in common disorders of the brain. In: Science. 2018 ; Vol. 360, No. 6395. pp. 1-15.
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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.",
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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

Analysis of shared heritability in common disorders of the brain. /; 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; Smith, Amanda G; Matthews, Keith; McIntosh, Andrew; Robertson, Mary M; Cohen, David.

In: Science, Vol. 360, No. 6395, eaap8757, 22.06.2018, p. 1-15.

Research output: Contribution to journalArticle

TY - JOUR

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

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

N1 - Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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

VL - 360

SP - 1

EP - 15

JO - Science

JF - Science

SN - 0036-8075

IS - 6395

M1 - eaap8757

ER -

Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J et al. Analysis of shared heritability in common disorders of the brain. Science. 2018 Jun 22;360(6395):1-15. eaap8757. https://doi.org/10.1126/science.aap8757