TY - JOUR T1 - Genome wide meta-analysis identifies genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders JF - bioRxiv DO - 10.1101/528117 SP - 528117 AU - Cross-Disorder Group of the Psychiatric Genomics Consortium AU - Phil H. Lee AU - Verneri Anttila AU - Hyejung Won AU - Yen-Chen A. Feng AU - Jacob Rosenthal AU - Zhaozhong Zhu AU - Elliot M. Tucker-Drob AU - Michel G. Nivard AU - Andrew D. Grotzinger AU - Danielle Posthuma AU - Meg M.-J. Wang AU - Dongmei Yu AU - Eli Stahl AU - Raymond K. Walters AU - Richard J.L. Anney AU - Laramie E. Duncan AU - Sintia Belangero AU - Jurjen Luykx AU - Henry Kranzler AU - Anna Keski-Rahkonen AU - Edwin H. Cook AU - George Kirov AU - Giovanni Coppola AU - Jaakko Kaprio AU - Clement C. Zai AU - Pieter J. Hoekstra AU - Tobias Banaschewski AU - Luis A. Rohde AU - PGC Attention Deficit Hyperactivity Disorder Group AU - PGC Autism Spectrum Disorder Group AU - PGC Bipolar Disorder Group AU - PGC Eating Disorders Group AU - PGC Major Depressive Disorder Group AU - PGC Obsessive Compulsive Disorder and Tourette Syndrome Group AU - PGC Schizophrenia Group AU - Patrick F. Sullivan AU - Barbara Franke AU - Mark J. Daly AU - Cynthia M. Bulik AU - Cathryn M. Lewis AU - Andrew M. McIntosh AU - Michael C. O’Donovan AU - Amanda Zheutlin AU - Ole A. Andreassen AU - Anders D. Borglum AU - Gerome Breen AU - Howard J. Edenberg AU - Ayman H. Fanous AU - Stephen V. Faraone AU - Joel Gelernter AU - Carol A. Mathews AU - Manuel Mattheisen AU - Karen Mitchell AU - Michael C. Neale AU - John I. Nurnberger AU - Stephan Ripke AU - Susan L. Santangelo AU - Jeremiah M. Scharf AU - Murray B. Stein AU - Laura M. Thornton AU - James T.R. Walters AU - Naomi R. Wray AU - Daniel H. Geschwind AU - Benjamin Neale AU - Kenneth S. Kendler AU - Jordan W. Smoller Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/01/26/528117.abstract 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 a meta-analysis 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. We 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 in the second trimester prenatally, and play prominent roles in a suite of neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction. ER -