Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Research output: Contribution to journal › Journal article › Research › peer-review

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Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. / Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

In: Cell, Vol. 179, No. 7, 2019, p. 1469-1482.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2019, 'Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders', Cell, vol. 179, no. 7, pp. 1469-1482. https://doi.org/10.1016/j.cell.2019.11.020

APA

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2019). Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. Cell, 179(7), 1469-1482. https://doi.org/10.1016/j.cell.2019.11.020

Vancouver

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. Cell. 2019;179(7):1469-1482. https://doi.org/10.1016/j.cell.2019.11.020

Author

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. / Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. In: Cell. 2019 ; Vol. 179, No. 7. pp. 1469-1482.

Bibtex

@article{240e080b05f04403b933f8f572cf923a,
title = "Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders",
abstract = "{\textcopyright} 2019 Elsevier Inc. Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.",
keywords = "cross-disorder genetics, functional genomics, gene expression, genetic architecture, genetic correlation, GWAS, neurodevelopment, pleiotropy, psychiatric disorders, Psychiatric genetics",
author = "Lee, {Phil H.} and Verneri Anttila and Hyejung Won and Feng, {Yen Chen A.} and Jacob Rosenthal and Zhaozhong Zhu and Tucker-Drob, {Elliot M.} and Nivard, {Michel G.} and Grotzinger, {Andrew D.} and Danielle Posthuma and Wang, {Meg M.J.} and Dongmei Yu and Stahl, {Eli A.} and Walters, {Raymond K.} and Anney, {Richard J.L.} and Duncan, {Laramie E.} and Tian Ge and Rolf Adolfsson and Tobias Banaschewski and Sintia Belangero and Cook, {Edwin H.} and Giovanni Coppola and Derks, {Eske M.} and Hoekstra, {Pieter J.} and Jaakko Kaprio and Anna Keski-Rahkonen and George Kirov and Kranzler, {Henry R.} and Luykx, {Jurjen J.} and Rohde, {Luis A.} and Zai, {Clement C.} and Esben Agerbo and Arranz, {M. J.} and Philip Asherson and Marie B{\ae}kvad-Hansen and G{\'i}sli Baldursson and Mark Bellgrove and Belliveau, {Richard A.} and Jan Buitelaar and Burton, {Christie L.} and Jonas Bybjerg-Grauholm and Miquel Casas and Felecia Cerrato and Kimberly Chambert and Claire Churchhouse and Hansen, {Christine S.} and Pedersen, {Carsten B.} and Pedersen, {Marianne G.} and Poulsen, {Jesper B.} and Thomas Werge and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium}",
year = "2019",
doi = "10.1016/j.cell.2019.11.020",
language = "English",
volume = "179",
pages = "1469--1482",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",

}

RIS

TY - JOUR

T1 - Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

AU - Lee, Phil H.

AU - Anttila, Verneri

AU - Won, Hyejung

AU - Feng, Yen Chen A.

AU - Rosenthal, Jacob

AU - Zhu, Zhaozhong

AU - Tucker-Drob, Elliot M.

AU - Nivard, Michel G.

AU - Grotzinger, Andrew D.

AU - Posthuma, Danielle

AU - Wang, Meg M.J.

AU - Yu, Dongmei

AU - Stahl, Eli A.

AU - Walters, Raymond K.

AU - Anney, Richard J.L.

AU - Duncan, Laramie E.

AU - Ge, Tian

AU - Adolfsson, Rolf

AU - Banaschewski, Tobias

AU - Belangero, Sintia

AU - Cook, Edwin H.

AU - Coppola, Giovanni

AU - Derks, Eske M.

AU - Hoekstra, Pieter J.

AU - Kaprio, Jaakko

AU - Keski-Rahkonen, Anna

AU - Kirov, George

AU - Kranzler, Henry R.

AU - Luykx, Jurjen J.

AU - Rohde, Luis A.

AU - Zai, Clement C.

AU - Agerbo, Esben

AU - Arranz, M. J.

AU - Asherson, Philip

AU - Bækvad-Hansen, Marie

AU - Baldursson, Gísli

AU - Bellgrove, Mark

AU - Belliveau, Richard A.

AU - Buitelaar, Jan

AU - Burton, Christie L.

AU - Bybjerg-Grauholm, Jonas

AU - Casas, Miquel

AU - Cerrato, Felecia

AU - Chambert, Kimberly

AU - Churchhouse, Claire

AU - Hansen, Christine S.

AU - Pedersen, Carsten B.

AU - Pedersen, Marianne G.

AU - Poulsen, Jesper B.

AU - Werge, Thomas

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

PY - 2019

Y1 - 2019

N2 - © 2019 Elsevier Inc. Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

AB - © 2019 Elsevier Inc. Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

KW - cross-disorder genetics

KW - functional genomics

KW - gene expression

KW - genetic architecture

KW - genetic correlation

KW - GWAS

KW - neurodevelopment

KW - pleiotropy

KW - psychiatric disorders

KW - Psychiatric genetics

U2 - 10.1016/j.cell.2019.11.020

DO - 10.1016/j.cell.2019.11.020

M3 - Journal article

C2 - 31835028

AN - SCOPUS:85076270049

VL - 179

SP - 1469

EP - 1482

JO - Cell

JF - Cell

SN - 0092-8674

IS - 7

ER -

ID: 236321870