Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

minor

Viola adunca Smithhooked violet;early blue violet;hooked-spur violet;sand violet;western dog violet;heath dog violetviolette à éperon crochuGillamDry soil of open cut-over and burned-over area (about 20 years ago).occasionalFlowers blue; laterals bearded. Plant quite glabrou

Miscellanies of Australian Sematophyllaceae with a new genus, Meiotheciella

Nova Hedwigia671-2213-223NOHE

The family Sematophyllaceae (Bryopsida) in Australia. Part 1: Introduction, family data, key to genera and the genera Wijkia, Acanthorrynchium, Trismegistia and Sematophyllum

Journal of the Hattori Botanical Laboratory921-5

The family Sematophyllaceae (Bryopsida) in Australia, part 2. Acroporium, Clastobryum, Macrohymenium, Meiotheciella, Meiothecium, Papillidiopsis, Radulina, Rhaphidorrhynchium, Trichosteleum, and Warburgiella

Journal of the Hattori Botanical Laboratory951-6

richardsonii

Achnatherum richardsonii (Link) BarkworthRichardson's needlegrassstipe de RichardsonStipa richardsoniiOn slope above east end of Pavilion Lake.Growing in limestone soil

comata

Hesperostipa comata (Trinius & Ruprecht) Barkworth subsp. comataneedle-and-thread grassstipe chevelueStipa comataAlong N.W. Pavilion LakeGrowing along roadside.Douglas fir, Phacelia linearis, Stipa columbian