Identifying tissues implicated in Anorexia Nervosa using Transcriptomic Imputation

Laura M. Huckins; Amanda Dobbyn; Whitney McFadden; Douglas Ruderfer; Weiqing Wang; Eric Gamazon; Virpi Leppä; Roger Adan; Tetsuya Ando; Jessica Baker; Andrew Bergen; Wade Berrettini; Andreas Birgegård; Claudette Boni; Vesna Boraska Perica; Harry Brandt; Roland Burghardt; Matteo Cassina; Carolyn Cesta; Maurizio Clementi; Joni Coleman; Roger Cone; Philippe Courtet; Steven Crawford; Scott Crow; James Crowley; Unna Danner; Oliver Davis; Martina de Zwaan; George Dedoussis; Daniela Degortes; Janiece DeSocio; Danielle Dick; Dimitris Dikeos; Monika Dmitrzak-Weglarz; Elisa Docampo; Karin Egberts; Stefan Ehrlich; Geòrgia Escaramís; Tonu Esko; Xavier Estivill; Favaro Angela; Fernando Fernández-Aranda; Manfred Fichter; Chris Finan; Krista Fischer; Lenka Foretova; Monica Forzan; Christopher Franklin; Héléna Gaspar; Fragiskos Gonidakis; Philip Gorwood; Gratacos Monica; Sébastien Guillaume; Yiran Guo; Hakon Hakonarson; Katherine Halmi; Konstantinos Hatzikotoulas; Joanna Hauser; Johannes Hebebrand; Sietske Helder; Judith Hendriks; Beate Herpertz-Dahlmann; Wolfgang Herzog; Christopher Hilliard; Anke Hinney; James Hudson; Julia Huemer; Hartmut Imgart; Hidetoshi Inoko; Susana Jiménez-Murcia; Craig Johnson; Jenny Jordan; Anders Juréus; Gursharan Kalsi; Debora Kaminska; Allan Kaplan; Jaakko Kaprio; Leila Karhunen; Andreas Karwautz; Martien Kas; Walter Kaye; James Kennedy; Martin Kennedy; Anna Keski-Rahkonen; Kirsty Kiezebrink; Youl-Ri Kim; Kelly Klump; Gun Peggy Knudsen; Bobby Koeleman; Doris Koubek; Maria La Via; Mikael Landén; Robert Levitan; Dong Li; Paul Lichtenstein; Lisa Lilenfeld; Jolanta Lissowska; Pierre Magistretti; Mario Maj; Katrin Mannik; Nicholas Martin; Sara McDevitt; Peter McGuffin; Elisabeth Merl; Andres Metspalu; Ingrid Meulenbelt; Nadia Micali; James Mitchell; Karen Mitchell; Palmiero Monteleone; Alessio Maria Monteleone; Preben Mortensen; Melissa Munn-Chernoff; Benedetta Nacmias; Ida Nilsson; Claes Norring; Ioanna Ntalla; Julie O'Toole; Jacques Pantel; Hana Papezova; Richard Parker; Raquel Rabionet; Anu Raevuori; Andrzej Rajewski; Nicolas Ramoz; N. William Rayner; Ted Reichborn-Kjennerud; Valdo Ricca; Stephan Ripke; Franziska Ritschel; Marion Roberts; Alessandro Rotondo; Filip Rybakowski; Paolo Santonastaso; André Scherag; Ulrike Schmidt; Nicholas Schork; Alexandra Schosser; Jochen Seitz; Lenka Slachtova; P. Eline Slagboom; Margarita Slof-Op ’t Landt; Agnieszka Slopien; Tosha Smith; Sandro Sorbi; Eric Strengman; Michael Strober; Patrick Sullivan; Jin Szatkiewicz; Neonila Szeszenia-Dabrowska; Ioanna Tachmazidou; Elena Tenconi; Laura Thornton; Alfonso Tortorella; Federica Tozzi; Janet Treasure; Artemis Tsitsika; Konstantinos Tziouvas; Annemarie van Elburg; Eric van Furth; Tracey Wade; Gudrun Wagner; Esther Walton; Hunna Watson; D. Blake Woodside; Shuyang Yao; Zeynep Yilmaz; Eleftheria Zeggini; Stephanie Zerwas; Stephan Zipfel; Alfredsson Lars; Andreassen Ole; Harald Aschauer; Jeffrey Barrett; Vladimir Bencko; Laura Carlberg; Sven Cichon; Sarah Cohen-Woods; Christian Dina; Bo Ding; Thomas Espeseth; James Floyd; Steven Gallinger; Giovanni Gambaro; Ina Giegling; Stefan Herms; Vladimir Janout; Antonio Juliá; Lars Klareskog; Stephanie Le Hellard; Marion Leboyer; Astri J. Lundervold; Sara Marsal; Morten Mattingsdal; Marie Navratilova; Roel Ophoff; Aarno Palotie; Dalila Pinto; Samuli Ripatti; Dan Rujescu; Stephen Scherer; Laura Scott; Robert Sladek; Nicole Soranzo; Lorraine Southam; Vidar Steen; Wichmann H-Erich; Elisabeth Widen; Bernie Devlin; Solveig K. Sieberts; Nancy Cox; Hae Kyung Im; Gerome Breen; Pamela Sklar; Cynthia Bulik; Eli A. Stahl

doi:10.1101/265017

Prépublication

Identifying tissues implicated in Anorexia Nervosa using Transcriptomic Imputation

Laura M. Huckins, Amanda Dobbyn, Whitney McFadden, Douglas Ruderfer, Weiqing Wang, Eric Gamazon, Virpi Leppä, Roger Adan, Tetsuya Ando, Jessica Baker, …

bioRxiv

Cold Spring Harbor Laboratory, 1.1

14/02/2018

DOI: https://doi.org/10.1101/265017

Résumé

Genetics

Anorexia nervosa (AN) is a complex and serious eating disorder, occurring in ~1% of individuals. Despite having the highest mortality rate of any psychiatric disorder, little is known about the aetiology of AN, and few effective treatments exist. Global efforts to collect large sample sizes of individuals with AN have been highly successful, and a recent study consequently identified the first genome-wide significant locus involved in AN. This result, coupled with other recent studies and epidemiological evidence, suggest that previous characterizations of AN as a purely psychiatric disorder are over-simplified. Rather, both neurological and metabolic pathways may also be involved. In order to elucidate more of the system-specific aetiology of AN, we applied transcriptomic imputation methods to 3,495 cases and 10,982 controls, collected by the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED). Transcriptomic Imputation (TI) methods approaches use machine-learning methods to impute tissue-specific gene expression from large genotype data using curated eQTL reference panels. These offer an exciting opportunity to compare gene associations across neurological and metabolic tissues. Here, we applied CommonMind Consortium (CMC) and GTEx-derived gene expression prediction models for 13 brain tissues and 12 tissues with potential metabolic involvement (adipose, adrenal gland, 2 colon, 3 esophagus, liver, pancreas, small intestine, spleen, stomach). We identified 35 significant gene-tissue associations within the large chromosome 12 region described in the recent PGC-ED GWAS. We applied forward stepwise conditional analyses and FINEMAP to associations within this locus to identify putatively causal signals. We identified four independently associated genes; RPS26, C12orf49, SUOX, and RDH16. We also identified two further genome-wide significant gene-tissue associations, both in brain tissues; REEP5, in the dorso-lateral pre-frontal cortex (DLPFC; p=8.52×10−07), and CUL3, in the caudate basal ganglia (p=1.8×10−06). These genes are significantly enriched for associations with anthropometric phenotypes in the UK BioBank, as well as multiple psychiatric, addiction, and appetite/satiety pathways. Our results support a model of AN risk influenced by both metabolic and psychiatric factors.

Indicateurs

1 Consultations de la notice

See more details

Détails

Titre: Identifying tissues implicated in Anorexia Nervosa using Transcriptomic Imputation
Créateurs - sans rôle: Laura M. Huckins - Icahn School of Medicine at Mount Sinai
Amanda Dobbyn - Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
Whitney McFadden - Department of Psychiatry, Icahn School of Medicine at Mount Sinai
Douglas Ruderfer - Vanderbilt University Medical Center
Weiqing Wang - Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai
Eric Gamazon - Section of Genetic Medicine, Department of Medicine, University of Chicago
Virpi Leppä - CEDI – Centre for Eating Disorders Innovation, Department of Medical Epidemiology and Biostatistics (MEB)
Roger Adan - Altrecht Eating Disorders Rintveld
Tetsuya Ando - National Institute of Mental Health
Jessica Baker - University of North Carolina at Chapel Hill
Andrew Bergen - BioRealm
Wade Berrettini - University of Pennsylvania
Andreas Birgegård - Stockholm Health Care Services
Claudette Boni - Centre of Psychiatry and Neuroscience
Vesna Boraska Perica - University of Split
Harry Brandt - Sheppard and Enoch Pratt Hospital
Roland Burghardt - Klinikum Frankfurt/Oder
Matteo Cassina - University of Padova
Carolyn Cesta - Karolinska Institutet
Maurizio Clementi - University of Padova
Joni Coleman - King’s College London
Roger Cone - University of Michigan
Philippe Courtet - CHRU Montpellier, University of Montpellier
Steven Crawford - Sheppard and Enoch Pratt Hospital
Scott Crow - University of Minnesota
James Crowley - Karolinska Institutet
Unna Danner - Altrecht Eating Disorders Rintveld
Oliver Davis - University of Bristol
Martina de Zwaan - Hannover Medical School
George Dedoussis - Harokopio University
Daniela Degortes - University of Padova
Janiece DeSocio - Seattle University
Danielle Dick - Virginia Commonwealth University
Dimitris Dikeos - Athens University Medical School
Monika Dmitrzak-Weglarz - Poznan University of Medical Sciences
Elisa Docampo - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Karin Egberts - Universitätsklinikum Würzburg
Stefan Ehrlich - Technische Universität Dresden
Geòrgia Escaramís - Centro de Investigación Biomédica en Red
Tonu Esko - University of Tartu
Xavier Estivill - Centre for Genomic Regulation
Favaro Angela - University of Padova
Fernando Fernández-Aranda - University Hospital of Bellvitge-IDIBELL and CIBEROBN, University of Barcelona
Manfred Fichter - Ludwig-Maximilians-Universität München
Chris Finan - Wellcome Trust Sanger Institute
Krista Fischer - University of Tartu
Lenka Foretova - Masaryk Memorial Cancer Institute
Monica Forzan - University Hospital of Padova
Christopher Franklin - Wellcome Sanger Institute
Héléna Gaspar - King’s College London
Fragiskos Gonidakis - National and Kapodistrian University of Athens
Philip Gorwood - INSERM U984, Sainte-Anne Hospital, University of Paris-Descartes
Gratacos Monica - Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública
Sébastien Guillaume - CHRU Montpellier, University of Montpellier
Yiran Guo - Children's Hospital of Philadelphia
Hakon Hakonarson - University of Pennsylvania
Katherine Halmi - Weill Cornell Medical College
Konstantinos Hatzikotoulas - Wellcome Sanger Institute
Joanna Hauser - Poznan University of Medical Sciences
Johannes Hebebrand - University of Duisburg-Essen
Sietske Helder - King's College London
Judith Hendriks - University Utrecht
Beate Herpertz-Dahlmann - RWTH Aachen University
Wolfgang Herzog - Heidelberg University
Christopher Hilliard - University of North Carolina at Chapel Hill
Anke Hinney - University of Duisburg-Essen
James Hudson - Harvard Medical School
Julia Huemer - Medical University of Vienna
Hartmut Imgart - Parkland-Klinik
Hidetoshi Inoko - Tokai University
Susana Jiménez-Murcia - University Hospital of Bellvitge-IDIBELL and CIBEROBN, University of Barcelona
Craig Johnson - The Recovery Center
Jenny Jordan - Canterbury District Health Board
Anders Juréus - Karolinska Institutet
Gursharan Kalsi - King's College London
Debora Kaminska - Charles University
Allan Kaplan - University of Toronto
Jaakko Kaprio - University of Helsinki
Leila Karhunen - University of Eastern Finland
Andreas Karwautz - Medical University of Vienna
Martien Kas - University Medical Center Utrecht
Walter Kaye - University of California
James Kennedy - University of Toronto
Martin Kennedy - University of Otago
Anna Keski-Rahkonen - University of Helsinki
Kirsty Kiezebrink - University of Aberdeen
Youl-Ri Kim - Inje University
Kelly Klump - Michigan State University
Gun Peggy Knudsen - Norwegian Institute of Public Health
Bobby Koeleman - University Medical Center Utrecht
Doris Koubek - Medical University of Vienna
Maria La Via - University of North Carolina at Chapel Hill
Mikael Landén - Karolinska Institutet
Robert Levitan - University of Toronto
Dong Li - Children’s Hospital of Philadelphia
Paul Lichtenstein - Karolinska Institutet
Lisa Lilenfeld - Argosy University
Jolanta Lissowska - M. Sklodowska-Curie Cancer Center and Institute of Oncology
Pierre Magistretti - Brain Mind Institute, EPFL, Center for Psychiatric Neuroscience, Department of Psychiatry – CHUV/UNIL
Mario Maj - University of Campania “Luigi Vanvitelli”
Katrin Mannik - University of Tartu
Nicholas Martin - QIMR Berghofer Medical Research Institute
Sara McDevitt - University College Cork
Peter McGuffin - Kings College London
Elisabeth Merl - Medical University of Vienna
Andres Metspalu - University of Tartu
Ingrid Meulenbelt - Leiden University
Nadia Micali - University of Geneva
James Mitchell - University of North Dakota
Karen Mitchell - Boston University School of Medicine
Palmiero Monteleone - University of Salerno
Alessio Maria Monteleone - University of Campania “Luigi Vanvitelli”
Preben Mortensen - Aarhus University
Melissa Munn-Chernoff - University of North Carolina at Chapel Hill
Benedetta Nacmias - Department Neuroscience, Psychology, Drug Research and Child Health, University of Florence
Ida Nilsson - Center for Molecular Medicine, Karolinska University Hospital
Claes Norring - Stockholm Health Care Services
Ioanna Ntalla - Harokopio University
Julie O'Toole - Kartini Clinic
Jacques Pantel - Centre for Psychiatry and Neuroscience
Hana Papezova - Charles University
Richard Parker - QIMR Berghofer Medical Research Institute
Raquel Rabionet - Centro de Investigación Biomédica en Red
Anu Raevuori - University of Helsinki
Andrzej Rajewski - Poznan University of Medical Sciences
Nicolas Ramoz - Centre for Psychiatry and Neuroscience
N. William Rayner - Wellcome Trust Centre for Human Genetics
Ted Reichborn-Kjennerud - University of Oslo
Valdo Ricca - University of Florence
Stephan Ripke - Charité Universtätsmedizin Berlin
Franziska Ritschel - Technische Universität Dresden
Marion Roberts - University of Auckland
Alessandro Rotondo - University of Pisa
Filip Rybakowski - Institute of Psychiatry and Neurology, University of Social Sciences and Humanities
Paolo Santonastaso - University of Padova
André Scherag - Jena University Hospital
Ulrike Schmidt - King’s College London
Nicholas Schork - J. Craig Venter Institute
Alexandra Schosser - Medical University of Vienna
Jochen Seitz - RWTH Aachen University
Lenka Slachtova - Charles University
P. Eline Slagboom - Leiden University
Margarita Slof-Op ’t Landt - Rivierduinen Eating Disorders Ursula, Leiden University Medical Centre
Agnieszka Slopien - Uniwersytet Medyczny im. Karola Marcinkowskiego
Tosha Smith - University of North Carolina at Chapel Hill
Sandro Sorbi - IRCSS Fondazione Don Gnocchi, Florence
Eric Strengman - Department of Pathology, University Medical Center Utrecht, The Netherlands
Michael Strober - University of California, Los Angeles
Patrick Sullivan - Karolinska Institutet
Jin Szatkiewicz - University of North Carolina at Chapel Hill
Neonila Szeszenia-Dabrowska - Nofer Institute of Occupational Medicine, Department of Environmental Epidemiology
Ioanna Tachmazidou - Wellcome Sanger Institute
Elena Tenconi - University of Padova
Laura Thornton - University of North Carolina at Chapel Hill
Alfonso Tortorella - University of Perugia
Federica Tozzi - University of Cyprus
Janet Treasure - King's College London
Artemis Tsitsika - University of Athens “P. & A. Kyriakou” Children’s Hospital
Konstantinos Tziouvas - “P. & A. Kyriakou” Children’s Hospital, PICU
Annemarie van Elburg - University of Utrecht
Eric van Furth - Leiden University Medical Center
Tracey Wade - Flinders University
Gudrun Wagner - Medical University of Vienna
Esther Walton - Technische Universität Dresden
Hunna Watson - School of Psychology and Speech Pathology, Faculty of Health Sciences, Curtin University
D. Blake Woodside - University of Toronto
Shuyang Yao - Karolinksa Institutet
Zeynep Yilmaz - University of North Carolina at Chapel Hill
Eleftheria Zeggini - Wellcome Trust Sanger Institute
Stephanie Zerwas - University of North Carolina at Chapel Hill
Stephan Zipfel - University Medical Hospital Tuebingen
Alfredsson Lars - Karolinska Institutet
Andreassen Ole - Oslo University Hospital
Harald Aschauer - Biopsychosocial Corporation
Jeffrey Barrett - Sanger Institute
Vladimir Bencko - Charles University, First Faculty of Medicine, Institute of Hygiene and Epidemiology
Laura Carlberg - Medical University of Vienna
Sven Cichon - University Hospital of Basel
Sarah Cohen-Woods - Finders University
Christian Dina - Nantes Université
Bo Ding - University of California at San Diego
Thomas Espeseth - Oslo University Hospital
James Floyd - Wellcome Trust Sanger Institute, Genomics PLC
Steven Gallinger - University of Toronto
Giovanni Gambaro - Columbus-Gemelli University Hospital
Ina Giegling - Martin Luther University Halle-Wittenberg
Stefan Herms - University of Basel
Vladimir Janout - Ostrava University
Antonio Juliá - Vail d'Hebron Hospital Research Institute
Lars Klareskog - Karolinska Institutet
Stephanie Le Hellard - Haukeland University Hospital
Marion Leboyer - Université Paris-Est-Créteil (UPEC)
Astri J. Lundervold - University of Bergen
Sara Marsal - Vail d'Hebron Hospital Research Institute
Morten Mattingsdal - Oslo University
Marie Navratilova - Masaryk Memorial Cancer Institute
Roel Ophoff - University of California, Los Angeles
Aarno Palotie - Institute for Molecular Medicine
Dalila Pinto - Icahn School of Medicine at Mount Sinai
Samuli Ripatti - University of Helsinki
Dan Rujescu - Ludwig-Maximilians-University Munich
Stephen Scherer - University of Toronto
Laura Scott - Department of Biostatistics, University of Michigan
Robert Sladek - Génome Québec Innovation Centre
Nicole Soranzo - University of Cambridge
Lorraine Southam - Wellcome Trust Centre for Human Genetics
Vidar Steen - Haukeland University Hospital
Wichmann H-Erich - Helmholtz Centre Munich - German Research Center for Environmental Health
Elisabeth Widen - Institute for Molecular Medicine
Bernie Devlin - Department of Psychiatry, University of Pittsburgh
Solveig K. Sieberts - Systems Biology, Sage Bionetworks
Nancy Cox - Section of Genetic Medicine, Department of Medicine, University of Chicago
Hae Kyung Im - Vanderbilt University Medical Center
Gerome Breen - King’s College London
Pamela Sklar - Icahn School of Medicine at Mount Sinai
Cynthia Bulik - Karolinska Institutet
Eli A. Stahl - Icahn School of Medicine at Mount Sinai
Détails de publication: bioRxiv
Éditeur: Cold Spring Harbor Laboratory
Édition: 1.1
Nombre de pages: 65
Identifiants: 99139485509311
Unité académique: Institut de Génomique Fonctionnelle - IGF
Langue: English; Japanese
Type de ressource: Preprint