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; Claudine Berr; Luc Letenneur; Didier Hannequin; Philippe Amouyel; Anne Boland; Jean-Francois 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; James B. Leverenz; Allan I. Levey; Andrew P. Lieberman; Vernon S. Pankratz; Wayne W. Poon; Klaus-Peter Lesch; Jim van Os; Brainstorm Consortium; Aiden Corvin; Benjamin M. Neale

doi:10.1126/science.aap8757

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, Claudine BerrLuc Letenneur, Didier Hannequin, Philippe Amouyel, Anne Boland, Jean-Francois 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, James B. Leverenz, Allan I. Levey, Andrew P. Lieberman, Vernon S. Pankratz, Wayne W. Poon, Klaus-Peter Lesch, Jim van Os, Brainstorm Consortium, Aiden Corvin^*, Benjamin M. Neale^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

818 Citations (Web of Science)

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	8757
Number of pages	13
Journal	Science
Volume	360
Issue number	6395
DOIs	https://doi.org/10.1126/science.aap8757
Publication status	Published - 22 Jun 2018

Keywords

GENOME-WIDE ASSOCIATION
DEFICIT HYPERACTIVITY DISORDER
MAJOR DEPRESSIVE DISORDER
POPULATION-BASED TWIN
LONG-TERM SURVIVAL
BODY-MASS INDEX
ALZHEIMERS-DISEASE
ANOREXIA-NERVOSA
BIPOLAR DISORDER
GENETIC CORRELATIONS
Genome-Wide Association Study
Quantitative Trait, Heritable
Humans
Risk Factors
Mental Disorders/classification
Genetic Variation
Phenotype
Brain Diseases/classification

Access to Document

10.1126/science.aap8757

http://discovery.dundee.ac.uk/ws/files/27601589/aap8757_MainText.pdf

Cite this

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., Kamatani, Y., ... Neale, B. M. (2018). Analysis of shared heritability in common disorders of the brain. Science, 360(6395), [8757]. https://doi.org/10.1126/science.aap8757

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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 = "GENOME-WIDE ASSOCIATION, DEFICIT HYPERACTIVITY DISORDER, MAJOR DEPRESSIVE DISORDER, POPULATION-BASED TWIN, LONG-TERM SURVIVAL, BODY-MASS INDEX, ALZHEIMERS-DISEASE, ANOREXIA-NERVOSA, BIPOLAR DISORDER, GENETIC CORRELATIONS, Genome-Wide Association Study, Quantitative Trait, Heritable, Humans, Risk Factors, Mental Disorders/classification, Genetic Variation, Phenotype, Brain Diseases/classification",

author = "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-Francois 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 Leverenz, {James B.} and Levey, {Allan I.} and Lieberman, {Andrew P.} and Pankratz, {Vernon S.} and Poon, {Wayne W.} and Klaus-Peter Lesch and {van Os}, Jim and {Brainstorm Consortium} and Aiden Corvin and Neale, {Benjamin M.}",

year = "2018",

month = jun,

day = "22",

doi = "10.1126/science.aap8757",

language = "English",

volume = "360",

journal = "Science",

issn = "0036-8075",

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

number = "6395",

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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, Leverenz, JB, Levey, AI, Lieberman, AP, Pankratz, VS, Poon, WW, Lesch, K-P, van Os, J, Brainstorm Consortium, Corvin, A & Neale, BM 2018, 'Analysis of shared heritability in common disorders of the brain', Science, vol. 360, no. 6395, 8757. https://doi.org/10.1126/science.aap8757

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-Francois

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 - Leverenz, James B.

AU - Levey, Allan I.

AU - Lieberman, Andrew P.

AU - Pankratz, Vernon S.

AU - Poon, Wayne W.

AU - Lesch, Klaus-Peter

AU - van Os, Jim

AU - Brainstorm Consortium

AU - Corvin, Aiden

AU - Neale, Benjamin M.

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 - GENOME-WIDE ASSOCIATION

KW - DEFICIT HYPERACTIVITY DISORDER

KW - MAJOR DEPRESSIVE DISORDER

KW - POPULATION-BASED TWIN

KW - LONG-TERM SURVIVAL

KW - BODY-MASS INDEX

KW - ALZHEIMERS-DISEASE

KW - ANOREXIA-NERVOSA

KW - BIPOLAR DISORDER

KW - GENETIC CORRELATIONS

KW - Genome-Wide Association Study

KW - Quantitative Trait, Heritable

KW - Humans

KW - Risk Factors

KW - Mental Disorders/classification

KW - Genetic Variation

KW - Phenotype

KW - Brain Diseases/classification

U2 - 10.1126/science.aap8757

DO - 10.1126/science.aap8757

M3 - Article

VL - 360

JO - Science

JF - Science

SN - 0036-8075

IS - 6395

M1 - 8757

ER -