Journal article

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

Phil H Lee, Verneri Anttila, Hyejung Won, Yen-Chen A Feng, Jacob Rosenthal, Zhaozhong Zhu, Elliot M Tucker-Drob, Michel G Nivard, Andrew D Grotzinger, Danielle Posthuma, Meg M-J Wang, Dongmei Yu, Eli A Stahl, Ray-mond K Walters, Richard JL Anney, Laramie E Duncan, Tian Ge, Rolf Adolfsson, Tobias Banaschewski, Sintia Belangero Show all

Cell | CELL PRESS | Published : 2019

Abstract

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 assoc..

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Grants

Awarded by Research Council of Norway


Awarded by South East Norway Health Authority


Awarded by Swedish Research Council (Vetenskapsradet)


Awarded by National Institute of Mental Health


Awarded by NIAAA


Awarded by Lundbeck Foundation


Awarded by Simons Foundation


Awarded by NIMH


Awarded by NIH


Awarded by ARRA


Awarded by NIH Genes, Environment, and Health Initiative [GEI]


Awarded by GENEVA Coordinating Center


Awarded by NIH GEI



Funding Acknowledgements

The work of the contributing groups was supported by numerous grants from governmental and charitable bodies as well as philanthropic donation. Specifically, P.H.L. (R00MH101367; R01MH119243), and J.W.S. (R01MH106547; R01MH117599; U01HG008685). The PGC has been supported by the following grants: MH085508, MH085513, MH085518, MH085520, MH094411, MH094421, MH094432, MH096296, MH109499, MH109501, MH109514, MH109528, MH109532, MH109536, MH109539. Funding for the work in Bipolar Disorder was supported by the Research Council of Norway (#223273, 248778, 262656, 273291, 283798, 248828), South East Norway Health Authority (2017-112), and KG Jebsen Stiftelsen. Funding for the work in eating disorders was supported by grants from the Klarman Family Foundation, Swedish Research Council (Vetenskapsradet: 538-2013-8864), National Institute of Mental Health (K01MH106675, K01 MH109782, K01MH100435, R01MH119084), and NIAAA (K01 AA025113). The iPSYCH project is supported by grants from the Lundbeck Foundation (R165-201315320, R102-A9118, R155-2014-1724 and R248-2017-2003) and the universities and university hospitals of Aarhus and Copenhagen. Genotyping of iPSYCH samples was suppozrted by grants from the Lundbeck Foundation, the Stanley Foundation, the Simons Foundation (SFARI 311789 to M.J.D.), and NIMH (5U01MH094432-02 to M.J.D.). The Danish National Biobank resource was supported by the Novo Nordisk Foundation. Data handling and analysis on the GenomeDK HPC facility was supported by NIMH (1U01MH109514-01 to A.D.B.). High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark (grant to ADB). Funding for the work in Tourette Syndrome/Obsessive Compulsive Disorder was supported by NIH grants U01NS040024, R01NS016648, K02NS085048, R01 MH096767, ARRA grants NS04002409S1 and NS040024-07S1, P30 NS062691, R01MH092293, R01MH092513, R01MH092289, R01MH071507, R01MH079489, R01MH079487, R01MH079488, R01MH079494, R01MH002930-06, R01MH073250, and MH087748, and grants from the Tourette Association of America and the David Judah Foundation. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment, and Health Initiative [GEI] (U01 HG004422); SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under the NIH GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of data sets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (P01 CA089392), and the Family Study of Cocaine Dependence (R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, NIDA, and the NIH contract "High Throughput Genotyping for Studying the Genetic Contributions to Human Disease'' (HHSN268200782096C). The data sets used for the analyses described here were obtained from dbGaP (https://www.ncbi.nlm.nih.gov/projects/gap/cgibin/study.cgi?study_id=phs000092.v1.r p1).All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We thank the research participants and employees of 23andMe, Inc. for their contribution to this study. We are grateful to Emily Madsen for assistance with manuscript preparation.