Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa

Laramie Duncan(King's College London), Zeynep Yılmaz(King's College London), Helena Gaspar(King's College London), Raymond K. Walters(King's College London), Jackie Goldstein(King's College London), Verneri Anttila(King's College London), Brendan Bulik‐Sullivan(King's College London), Stephan Ripke(King's College London), Laura Thornton(King's College London), Anke Hinney(King's College London), Mark J. Daly(King's College London), Patrick F. Sullivan(King's College London), Eleftheria Zeggini(King's College London), Gerome Breen(King's College London), Cynthia M. Bulik(King's College London), Laramie Duncan(King's College London), Zeynep Yılmaz(King's College London), Héléna A. Gaspar(King's College London), Raymond K. Walters(King's College London), Jackie Goldstein(King's College London), Verneri Anttila(King's College London), Brendan Bulik‐Sullivan(King's College London), Stephan Ripke(King's College London), Roger A.H. Adan(Genomics (United Kingdom)), Lars Alfredsson(Genomics (United Kingdom)), Tetsuya Ando(Genomics (United Kingdom)), Ole A. Andreassen(Genomics (United Kingdom)), H.N. Aschauer(Genomics (United Kingdom)), Jessica H. Baker(Genomics (United Kingdom)), Jeffrey C. Barrett(Genomics (United Kingdom)), Vladimír Bencko(Genomics (United Kingdom)), Andrew W. Bergen(Genomics (United Kingdom)), Wade Berrettini(Genomics (United Kingdom)), Andreas Birgegård(Genomics (United Kingdom)), Claudette Boni(Genomics (United Kingdom)), Vesna Boraska Perica(Genomics (United Kingdom)), Harry Brandt(Genomics (United Kingdom)), Roland Burghardt(Genomics (United Kingdom)), Laura Carlberg(Genomics (United Kingdom)), Matteo Cassina(Genomics (United Kingdom)), Carolyn E. Cesta(Genomics (United Kingdom)), Sven Cichon(Genomics (United Kingdom)), Maurizio Clementi(Genomics (United Kingdom)), Sarah Cohen‐Woods(Genomics (United Kingdom)), Joni Coleman(Genomics (United Kingdom)), Roger D. Cone(Genomics (United Kingdom)), Philippe Courtet(Genomics (United Kingdom)), Steven Crawford(Genomics (United Kingdom)), Scott J. Crow(Genomics (United Kingdom)), Jim Crowley(Genomics (United Kingdom)), Unna N. Danner(Genomics (United Kingdom)), Oliver S. P. Davis(Genomics (United Kingdom)), Martina de Zwaan(Genomics (United Kingdom)), George Dedoussis(Genomics (United Kingdom)), Daniela Degortes(Genomics (United Kingdom)), Janiece E. DeSocio(Genomics (United Kingdom)), Danielle M. Dick(Genomics (United Kingdom)), Dimitris Dikeos(Genomics (United Kingdom)), Christian Dina(Genomics (United Kingdom)), Bo Ding(Genomics (United Kingdom)), Monika Dmitrzak‐Węglarz(Genomics (United Kingdom)), Elisa Docampo(Genomics (United Kingdom)), Karin Egberts(Genomics (United Kingdom)), Stefan Ehrlich(Genomics (United Kingdom)), Geòrgia Escaramís(Genomics (United Kingdom)), Tõnu Esko(Genomics (United Kingdom)), Thomas Espeseth(Genomics (United Kingdom)), Xavier Estivill(Genomics (United Kingdom)), Angela Favaro(Genomics (United Kingdom)), Fernando Fernández‐Aranda(Genomics (United Kingdom)), Manfred Fichter(Genomics (United Kingdom)), Chris Finan(Genomics (United Kingdom)), Krista Fischer(Genomics (United Kingdom)), James Floyd(Genomics (United Kingdom)), Manuel Föcker(Genomics (United Kingdom)), Lenka Foretová(Genomics (United Kingdom)), Monica Forzan(Genomics (United Kingdom)), Caroline S. Fox(Genomics (United Kingdom)), C. Franklin(Genomics (United Kingdom)), Valérie Gaborieau(Genomics (United Kingdom)), Steven Gallinger(Genomics (United Kingdom)), Giovanni Gambaro(Genomics (United Kingdom)), Ina Giegling(Genomics (United Kingdom)), Fragiskos Gonidakis(Genomics (United Kingdom)), Philip Gorwood(Genomics (United Kingdom)), Mónica Gratacòs(Genomics (United Kingdom)), Sébastien Guillaume(Genomics (United Kingdom)), Yiran Guo(Genomics (United Kingdom)), Hakon Hakonarson(Genomics (United Kingdom)), Katherine A. Halmi(Genomics (United Kingdom)), Rebecca Harrison(Genomics (United Kingdom)), Konstantinos Hatzikotoulas(Genomics (United Kingdom)), Joanna Hauser(Genomics (United Kingdom)), Johannes Hebebrand(Genomics (United Kingdom)), Sietske G. Helder(Genomics (United Kingdom)), Judith Hendriks(Genomics (United Kingdom)), Stefan Herms(Genomics (United Kingdom)), Beate Herpertz‐Dahlmann(Genomics (United Kingdom)), Wolfgang Herzog(Genomics (United Kingdom)), Christopher Hilliard(Genomics (United Kingdom)), Laura M. Huckins(Genomics (United Kingdom)), James I. Hudson(Genomics (United Kingdom)), Julia Huemer(Genomics (United Kingdom)), Hartmut Imgart, Hidetoshi Inoko(Genomics (United Kingdom)), Sigrid Jall(Genomics (United Kingdom)), Stéphane Jamain(Genomics (United Kingdom)), Vladimí­r Janout(Genomics (United Kingdom)), Susana Jiménez‐Múrcia(Genomics (United Kingdom)), Craig Johnson(Genomics (United Kingdom)), Jenny Jordan(Genomics (United Kingdom)), Antonio Julià(Genomics (United Kingdom)), Anders Juréus(Genomics (United Kingdom)), Gursharan Kalsi(Genomics (United Kingdom)), Allan S. Kaplan(Genomics (United Kingdom)), Jaakko Kaprio(Genomics (United Kingdom)), Leila Karhunen(Genomics (United Kingdom)), Andreas Karwautz(Genomics (United Kingdom)), Martien J. Kas(Genomics (United Kingdom)), Walter H. Kaye(Genomics (United Kingdom)), Martin A. Kennedy(Genomics (United Kingdom)), James L. Kennedy(Genomics (United Kingdom)), Anna Keski‐Rahkonen(Genomics (United Kingdom)), Kirsty Kiezebrink(Genomics (United Kingdom)), Youl‐Ri Kim(Genomics (United Kingdom)), Lars Klareskog(Genomics (United Kingdom)), Kelly L. Klump(Genomics (United Kingdom)), Gun Peggy Knudsen(Genomics (United Kingdom)), Bobby P.C. Koeleman(Genomics (United Kingdom)), Doris Koubek(Genomics (United Kingdom)), Maria La Via(Genomics (United Kingdom)), Mikael Landén(Genomics (United Kingdom)), Stéphanie Le Hellard(Genomics (United Kingdom)), Marion Leboyer(Genomics (United Kingdom)), Robert D. Levitan(Genomics (United Kingdom)), Dong Li(Genomics (United Kingdom)), Paul Lichtenstein(Genomics (United Kingdom)), Lisa Lilenfeld(Genomics (United Kingdom)), Jolanta Lissowska(Genomics (United Kingdom)), Astri J. Lundervold(Genomics (United Kingdom)), Pierre J. Magistretti(Genomics (United Kingdom)), Mario Maj(Genomics (United Kingdom)), Katrin Männik(Genomics (United Kingdom)), Sara Marsal(Genomics (United Kingdom)), Debora Kaminska(Genomics (United Kingdom)), Nicholas G. Martin(Genomics (United Kingdom)), Morten Mattingsdal(Genomics (United Kingdom)), Sara McDevitt(Genomics (United Kingdom)), Peter McGuffin(Genomics (United Kingdom)), Elisabeth Merl(Genomics (United Kingdom)), Andres Metspalu(Genomics (United Kingdom)), Ingrid Meulenbelt(Genomics (United Kingdom)), Nadia Micali(Genomics (United Kingdom)), James E. Mitchell(Genomics (United Kingdom)), Karen S. Mitchell(Genomics (United Kingdom)), Palmiero Monteleone(Genomics (United Kingdom)), Alessio Maria Monteleone(Genomics (United Kingdom)), Grant W. Montgomery(Genomics (United Kingdom)), Preben Bo Mortensen, Melissa A. Munn‐Chernoff(Genomics (United Kingdom)), Timo D. Müller(Genomics (United Kingdom)), Benedetta Nacmias(Genomics (United Kingdom)), Marie Navratilova(Genomics (United Kingdom)), Ida Nilsson(Genomics (United Kingdom)), Claes Norring(Genomics (United Kingdom)), Ιωάννα Ντάλλα(Genomics (United Kingdom)), Roel A. Ophoff(Genomics (United Kingdom)), Julie O’Toole(Genomics (United Kingdom)), Aarno Palotie(Genomics (United Kingdom)), Jacques Pantel(Genomics (United Kingdom)), Hana Papežová(Genomics (United Kingdom)), Richard Parker(Genomics (United Kingdom)), Dalila Pinto(Genomics (United Kingdom)), Raquel Rabionet(Genomics (United Kingdom)), Anu Raevuori(Genomics (United Kingdom)), Andrzej Rajewski(Genomics (United Kingdom)), Nicolás Ramoz(Genomics (United Kingdom)), N. William Rayner(Genomics (United Kingdom)), Ted Reichborn‐Kjennerud(Genomics (United Kingdom)), Valdo Ricca(Genomics (United Kingdom)), Samuli Ripatti(Genomics (United Kingdom)), Franziska Ritschel(Genomics (United Kingdom)), Marion Roberts(Genomics (United Kingdom)), Alessandro Rotondo(Genomics (United Kingdom)), Dan Rujescu(Genomics (United Kingdom)), Filip Rybakowski(Genomics (United Kingdom)), Paolo Santonastaso(Genomics (United Kingdom)), André Scherag(Genomics (United Kingdom)), Stephen W. Scherer(Genomics (United Kingdom)), Ulrike Schmidt(Genomics (United Kingdom)), Nicholas J. Schork(Genomics (United Kingdom)), Alexandra Schosser(Genomics (United Kingdom)), Laura J. Scott(Genomics (United Kingdom)), Jochen Seitz(Genomics (United Kingdom)), Lenka Šlachtová(Genomics (United Kingdom)), Robert Sladek(Genomics (United Kingdom)), P. Eline Slagboom, M Landt(Genomics (United Kingdom)), Agnieszka Slopien(Genomics (United Kingdom)), Tosha Smith(Genomics (United Kingdom)), Nicole Soranzo(Genomics (United Kingdom)), Sandro Sorbi(Genomics (United Kingdom)), Lorraine Southam(Genomics (United Kingdom)), Vidar M. Steen(Genomics (United Kingdom)), Eric Strengman(Genomics (United Kingdom)), Michael Strober(Genomics (United Kingdom)), Jin P. Szatkiewicz(Genomics (United Kingdom)), Neonila Szeszenia‐Dąbrowska(Genomics (United Kingdom)), Ioanna Tachmazidou(Genomics (United Kingdom)), Elena Tenconi(Genomics (United Kingdom)), Alfonso Tortorella(Genomics (United Kingdom)), Federica Tozzi(Genomics (United Kingdom)), Janet Treasure(Genomics (United Kingdom)), Matthias H. Tschöp(Genomics (United Kingdom)), Άρτεμις Τσίτσικα(Genomics (United Kingdom)), Konstantinos Tziouvas(Genomics (United Kingdom)), Annemarie van Elburg(Genomics (United Kingdom)), Eric F. van Furth(Genomics (United Kingdom)), Tracey Wade(Genomics (United Kingdom)), Gudrun Wagner(Genomics (United Kingdom)), Esther Walton(Genomics (United Kingdom)), Hunna J. Watson(Genomics (United Kingdom)), H‐Erich Wichmann(Genomics (United Kingdom)), Elisabeth Widén(Genomics (United Kingdom)), D. Blake Woodside(Genomics (United Kingdom)), Jack A. Yanovski(Genomics (United Kingdom)), Shuyang Yao(Genomics (United Kingdom)), Stephanie Zerwas(Genomics (United Kingdom)), Stephan Zipfel(Genomics (United Kingdom)), Laura Thornton(King's College London), Anke Hinney(King's College London), Mark J. Daly(King's College London), Patrick F. Sullivan(King's College London), Eleftheria Zeggini(King's College London), Gerome Breen(King's College London), Cynthia M. Bulik(King's College London)
American Journal of Psychiatry
May 12, 2017
Cited by 597Open Access
Full Text

Abstract

OBJECTIVE: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. METHOD: ) between anorexia nervosa and 159 other phenotypes. RESULTS: of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. CONCLUSIONS: Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.


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