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-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; Thomas Hansen; Thomas Werge; Jes Olesen; Rikke S Møller; Kerstin Plessen; Søren Dalsgaard; Brainstorm Consortium

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-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, Thomas Hansen, Thomas Werge, Jes Olesen, Rikke S Møller, Kerstin Plessen, Søren Dalsgaard, Brainstorm Consortium

1389 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Science
Vol/bind	360
Udgave nummer	6395
ISSN	0036-8075
DOI	https://doi.org/10.1126/science.aap8757
Status	Udgivet - 22 jun. 2018

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10.1126/science.aap8757

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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., ... Brainstorm Consortium (2018). Analysis of shared heritability in common disorders of the brain. Science, 360(6395). https://doi.org/10.1126/science.aap8757

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, Hansen, T , Werge, T , Olesen, J , Møller, RS , Plessen, K , Dalsgaard, S & Brainstorm Consortium 2018, 'Analysis of shared heritability in common disorders of the brain', Science, bind 360, nr. 6395. https://doi.org/10.1126/science.aap8757

@article{647354abc6be4c2a80c6a6a389f6a103,

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.",

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-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 Thomas Hansen and Thomas Werge and Jes Olesen and M{\o}ller, {Rikke S} and Kerstin Plessen and S{\o}ren Dalsgaard and {Brainstorm Consortium}",

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",

journal = "Science",

issn = "0036-8075",

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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 - Hansen, Thomas

AU - Werge, Thomas

AU - Olesen, Jes

AU - Møller, Rikke S

AU - Plessen, Kerstin

AU - Dalsgaard, Søren

AU - Brainstorm Consortium

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.

U2 - 10.1126/science.aap8757

DO - 10.1126/science.aap8757

M3 - Journal article

C2 - 29930110

SN - 0036-8075

VL - 360

JO - Science

JF - Science

IS - 6395

ER -

Analysis of shared heritability in common disorders of the brain

Abstract

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