TY - JOUR
T1 - Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
AU - Wellcome Trust Case Control Consortium
AU - Cross-Disorder Group of the Psychiatric Genomics Consortium
AU - 23andMe Research Team
AU - Psychosis Endophenotypes International Consortium
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 - Cormand, Bru
AU - Crosbie, Jennifer
AU - Dalsgaard, Søren
AU - Ikeda, Masashi
AU - Iwata, Nakao
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/12/12
Y1 - 2019/12/12
N2 - 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 - 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 - GWAS
KW - Psychiatric genetics
KW - cross-disorder genetics
KW - functional genomics
KW - gene expression
KW - genetic architecture
KW - genetic correlation
KW - neurodevelopment
KW - pleiotropy
KW - psychiatric disorders
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U2 - 10.1016/j.cell.2019.11.020
DO - 10.1016/j.cell.2019.11.020
M3 - Article
C2 - 31835028
AN - SCOPUS:85076270049
SN - 0092-8674
VL - 179
SP - 1469-1482.e11
JO - Cell
JF - Cell
IS - 7
ER -