Genome-Wide Association Study Reveals First Locus for Anorexia Nervosa and Metabolic Correlations

Laramie Duncan; Zeynep Yilmaz; Raymond Walters; Jackie Goldstein; Verneri Anttila; Brendan Bulik-Sullivan; Stephan Ripke; Roger Adan; Lars Alfredsson; Tetsuya Ando; Ole Andreassen; Harald Aschauer; Jessica Baker; Jeffrey Barrett; Vladimir Bencko; Andrew Bergen; Wade Berrettini; Andreas Birgegard; Claudette Boni; Vesna Perica; Harry Brandt; Roland Bughardt; Laura Carlberg; Matteo Cassina; Carolyn Cesta; Sven Cichon; Maurizio Clementi; Sarah Cohen-Woods; Joni Coleman; Roger Cone; Philippe Courtet; Steven Crawford; Scott Crow; Jim Crowley; Unna Danner; Oliver Davis; Martia De Zaan; George Dedoussis; Daniela Degortes; Janiece Desocio; Danielle Dick; Dimitris Dikeos; Dina Christian; Bo Ding; Monika Dmitrzak-Weglarz; Elisa Docampo; Karin Egberts; Stefan Ehrlich; Georgia Escaramis; Tonu Esko; Thomas Espeseth; Xavier Estivill; Angela Favaro; Fernando Fernandez-Aranda; Manfred Fichter; Chris Finan; Krista Fischer; James Floyd; Manuel Focker; Lenka etova; Monica zan; Caroline Fox; Christopher Franklin; Valerie Bagorieau; Steven Gallinger; Giovanni Gambaro; Helena Gaspar; Ina Giegling; Fragiskos Gonidakis; Philip Gorwood; Monica Gratacos; Sebastien Guillaume; Yiran Guo; Hakon Hakonarson; Katherine Halmi; Rebecca Harrison; Konstantinos Hatzikotoulas; Hoanna Hauser; Johannes Hebebrand; Sietske Helder; Judith Hendriks; Stefan Herms; Beate Herpertz-Dahlmann; Wolfgang Herzog; Christopher Hilliard; Laura Huckins; James Hudson; Julia Huemer; Hartmut Imgart; Hidetoshi Inoko; Sigrid Jall; Vladimir Janout; Susana Jimenez-Murcia; Jenny Jordan; Julia Antonio; Anders Jureus; Gursharan Kalsi; Allan Kaplan; Leila Karhunen; Andreas Karwautz; Martien Kas; Walter Kaye; Martin Kennedy; James Kennedy; Anna Keski-Rahkonen; Kirsty Kiezebrink; Youl-Ri Kim; Lars Klareskog; Kelly Klump; Gun Knudsen; Bobby Koeleman; Doris Koubek; Maria La Via; Mikael Landen; Stephanie Le Hellard; Robert Levitan; Dong Li; Paul Lichtenstein; Lisa Lilenfeld; Jolanta Lissowska; Astri Lundervold; Pierre Magistretti; Mario Maj; Katrin Mannik; Debora Kaminska; Nicholas Martin; Morten Mattingsdal; Sara Mcdevitt; Peter Mcguffin; Elisabeth Merl; Andres Metspalu; Ingrid Meulenbelt; Nadia Micali; James Mitchell; Karen Mitchell; Palmiero Monteleone; Alessio Monteleone; Grant Montgomery; Preben Mortensen; Melissa Munn-Chernoff; Timo Muller; Benedetta Nacmias; Marie Navratilova; Ida Nilsson; Claes Norring; Ioanna Ntalla; Roel Ophoff; Julie O'toole; Aarno Palotie; Jacques Pantel; Hana Papezova; Richard Parker; Dalila Pinto; Raquel Rabionet; Anu Raevuori; Andrzej Rajewski; Nicolas Ramoz; N Rayner; Ted Reichborn-Kjennerud; Valdo Ricca; Samuli Ripatti; Franziska Ritschel; Marion Roberts; Alessandro Rotondo; Dan Rujescu; Filip Rybakowski; Paolo Santonastaso; Andre Scherag; Stephen Scherer; Ulrike Schmidt; Nicholas Schork; Alexandra Schosser; Jochen Seitz; Lenka Slachtova; Robert Sladek; P Eline Slagboom; Margarita Slof-Op 't Landt; Agnieszka Slopien; Nicole Soranzo; Sandro Sorbi; Lorraine Southam; Vidar Steen; Michael Strober; Jin Szatkiewicz; Neonila Szeszenia-Dabrowska; Ioanna Tachmazidou; Elena Tenconi; Alfonso Tortorella; Federica Tozzi; Janet Treasure; Matthias Tschop; Artemis Tsitsika; Konstantinos Tziouvas; Annemarie Van Elburg; Eric Van Furth; Tracey Wade; Gudrun Wagner; Esther Walton; Hunna Watson; H-Erich Wichmann; Elisabeth Widen; D Blake Woodside; Jack Yanovski; Shuyang Yao; Stephanie Zerwas; Stephan Zipfel; Laura Thornton; Anke Hinney; Mark Daly; Patrick Sullivan; Eleftheria Zeggini; Gerome Breen; Cynthia Bulik

doi:10.1101/088815

Prépublication

Genome-Wide Association Study Reveals First Locus for Anorexia Nervosa and Metabolic Correlations

Laramie Duncan, Zeynep Yilmaz, Raymond Walters, Jackie Goldstein, Verneri Anttila, Brendan Bulik-Sullivan, Stephan Ripke, Roger Adan, Lars Alfredsson, Tetsuya Ando, …

bioRxiv

Cold Spring Harbor Laboratory Press

06/12/2016

DOI: https://doi.org/10.1101/088815

Résumé

Anorexia

Body mass

Body weight

Cholesterol

Eating disorders

Energy intake

Genetic diversity

Genome-wide association studies

Genomes

Heritability

High density lipoprotein

Insulin

Mental disorders

Metabolism

Morbidity

Neurosis

Phenotypes

Schizophrenia

Single-nucleotide polymorphism

Twins

Anorexia nervosa (AN) is a serious eating disorder characterized by restriction of energy intake relative to requirements, resulting in abnormally low body weight. It has a lifetime prevalence of approximately 1%, disproportionately affects females(1,2), and has no well replicated evidence of effective pharmacological or psychological treatments despite high morbidity and mortality(2). Twin studies support a genetic basis for the observed aggregation of AN in families(3), with heritability estimates of 48%-74%(4). Although initial genome-wide association studies (GWASs) were underpowered(5,6), evidence suggested that signals for AN would be detected with increased power(5). We present a GWAS of 3,495 AN cases and 10,982 controls with one genome-wide significant locus (index variant rs4622308, p=4.3x10-9) in a region (chr12:56,372,585-56,482,185) which includes six genes. The SNP-chip heritability (h_SNP^2) of AN from these data is 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability stems from common genetic variation. Using these GWAS results, we also find significant positive genetic correlations with schizophrenia, neuroticism, educational attainment, and HDL cholesterol, and significant negative genetic correlations with body mass, insulin, glucose, and lipid phenotypes. Our results support the reconceptualization of AN as a disorder with both psychiatric and metabolic components.

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Titre: Genome-Wide Association Study Reveals First Locus for Anorexia Nervosa and Metabolic Correlations
Créateurs - sans rôle: Laramie Duncan
Zeynep Yilmaz
Raymond Walters
Jackie Goldstein
Verneri Anttila
Brendan Bulik-Sullivan
Stephan Ripke
Roger Adan
Lars Alfredsson
Tetsuya Ando
Ole Andreassen
Harald Aschauer
Jessica Baker
Jeffrey Barrett
Vladimir Bencko
Andrew Bergen
Wade Berrettini
Andreas Birgegard
Claudette Boni
Vesna Perica
Harry Brandt
Roland Bughardt
Laura Carlberg
Matteo Cassina
Carolyn Cesta
Sven Cichon
Maurizio Clementi
Sarah Cohen-Woods
Joni Coleman
Roger Cone
Philippe Courtet
Steven Crawford
Scott Crow
Jim Crowley
Unna Danner
Oliver Davis
Martia De Zaan
George Dedoussis
Daniela Degortes
Janiece Desocio
Danielle Dick
Dimitris Dikeos
Dina Christian
Bo Ding
Monika Dmitrzak-Weglarz
Elisa Docampo
Karin Egberts
Stefan Ehrlich
Georgia Escaramis
Tonu Esko
Thomas Espeseth
Xavier Estivill
Angela Favaro
Fernando Fernandez-Aranda
Manfred Fichter
Chris Finan
Krista Fischer
James Floyd
Manuel Focker
Lenka etova
Monica zan
Caroline Fox
Christopher Franklin
Valerie Bagorieau
Steven Gallinger
Giovanni Gambaro
Helena Gaspar
Ina Giegling
Fragiskos Gonidakis
Philip Gorwood
Monica Gratacos
Sebastien Guillaume
Yiran Guo
Hakon Hakonarson
Katherine Halmi
Rebecca Harrison
Konstantinos Hatzikotoulas
Hoanna Hauser
Johannes Hebebrand
Sietske Helder
Judith Hendriks
Stefan Herms
Beate Herpertz-Dahlmann
Wolfgang Herzog
Christopher Hilliard
Laura Huckins
James Hudson
Julia Huemer
Hartmut Imgart
Hidetoshi Inoko
Sigrid Jall
Vladimir Janout
Susana Jimenez-Murcia
Jenny Jordan
Julia Antonio
Anders Jureus
Gursharan Kalsi
Allan Kaplan
Leila Karhunen
Andreas Karwautz
Martien Kas
Walter Kaye
Martin Kennedy
James Kennedy
Anna Keski-Rahkonen
Kirsty Kiezebrink
Youl-Ri Kim
Lars Klareskog
Kelly Klump
Gun Knudsen
Bobby Koeleman
Doris Koubek
Maria La Via
Mikael Landen
Stephanie Le Hellard
Robert Levitan
Dong Li
Paul Lichtenstein
Lisa Lilenfeld
Jolanta Lissowska
Astri Lundervold
Pierre Magistretti
Mario Maj
Katrin Mannik
Debora Kaminska
Nicholas Martin
Morten Mattingsdal
Sara Mcdevitt
Peter Mcguffin
Elisabeth Merl
Andres Metspalu
Ingrid Meulenbelt
Nadia Micali
James Mitchell
Karen Mitchell
Palmiero Monteleone
Alessio Monteleone
Grant Montgomery
Preben Mortensen
Melissa Munn-Chernoff
Timo Muller
Benedetta Nacmias
Marie Navratilova
Ida Nilsson
Claes Norring
Ioanna Ntalla
Roel Ophoff
Julie O'toole
Aarno Palotie
Jacques Pantel
Hana Papezova
Richard Parker
Dalila Pinto
Raquel Rabionet
Anu Raevuori
Andrzej Rajewski
Nicolas Ramoz
N Rayner
Ted Reichborn-Kjennerud
Valdo Ricca
Samuli Ripatti
Franziska Ritschel
Marion Roberts
Alessandro Rotondo
Dan Rujescu
Filip Rybakowski
Paolo Santonastaso
Andre Scherag
Stephen Scherer
Ulrike Schmidt
Nicholas Schork
Alexandra Schosser
Jochen Seitz
Lenka Slachtova
Robert Sladek
P Eline Slagboom
Margarita Slof-Op 't Landt
Agnieszka Slopien
Nicole Soranzo
Sandro Sorbi
Lorraine Southam
Vidar Steen
Michael Strober
Jin Szatkiewicz
Neonila Szeszenia-Dabrowska
Ioanna Tachmazidou
Elena Tenconi
Alfonso Tortorella
Federica Tozzi
Janet Treasure
Matthias Tschop
Artemis Tsitsika
Konstantinos Tziouvas
Annemarie Van Elburg
Eric Van Furth
Tracey Wade
Gudrun Wagner
Esther Walton
Hunna Watson
H-Erich Wichmann
Elisabeth Widen
D Blake Woodside
Jack Yanovski
Shuyang Yao
Stephanie Zerwas
Stephan Zipfel
Laura Thornton
Anke Hinney
Mark Daly
Patrick Sullivan
Eleftheria Zeggini
Gerome Breen
Cynthia Bulik
Détails de publication: bioRxiv
Éditeur: Cold Spring Harbor Laboratory Press; Cold Spring Harbor
Identifiants: 99139592709311
Unité académique: Institut de Génomique Fonctionnelle - IGF
Langue: English; Japanese
Type de ressource: Preprint