A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
Authors: Li Dong , Chang Xiao , Connolly John J. , Tian Lifeng , Liu Yichuan , Bhoj Elizabeth J. , Robinson Nora , Abrams Debra , Li Yun R. , Bradfield Jonathan P. , Kim Cecilia E. , Li Jin , Wang Fengxiang , Snyder James , Lemma Maria , Hou Cuiping , Wei Zhi , Guo Yiran , Qiu Haijun , Mentch Frank D. , Thomas Kelly A. , Chiavacci Rosetta M. , Cone Roger , Li Bingshan , Sleiman Patrick A. ,   Eating Disorders Working Group of the Psychiatric Genomics Consortium, Boraska Perica Vesna , Franklin Christopher S. , Floyd James A. B. , Thornton Laura M. , Huckins Laura M. , Southam Lorraine , Rayner N. William , Tachmazidou Ioanna , Klump Kelly L. , Treasure Janet , Schmidt Ulrike , Tozzi Federica , Kiezebrink Kirsty , Hebebrand Johannes , Gorwood Philip , Adan Roger A. H. , Kas Martien J. H. , Favaro Angela , Santonastaso Paolo , Fernánde-Aranda Fernando , Gratacos Monica , Rybakowski Filip , Dmitrzak-Weglarz Monika , Kaprio Jaakko , Keski-Rahkonen Anna , Raevuori-Helkamaa Anu , Van Furth Eric F. , Slof-Op’t Landt Margarita C. T. , Hudson James I. , Reichborn-Kjennerud Ted , Knudsen Gun Peggy S. , Monteleone Palmiero , Kaplan Allan S. , Karwautz Andreas , Berrettini Wade H. , Schork Nicholas J. , Ando Tetsuya , Inoko Hidetoshi , Esko Tõnu , Fischer Krista , Männik Katrin , Metspalu Andres , Baker Jessica H. , DeSocio Janiece E. , Hilliard Christopher E. , O’Toole Julie K. , Pantel Jacques , Szatkiewicz Jin P. , Zerwas Stephanie , Davis Oliver S. P. , Helder Sietske , Bühren Katharina , Burghardt Roland , de Zwaan Martina , Egberts Karin , Ehrlich Stefan , Herpertz-Dahlmann Beate , Herzog Wolfgang , Imgart Hartmut , Scherag André , Zipfel Stephan , Boni Claudette , Ramoz Nicolas , Versini Audrey , Danner Unna N. , Hendriks Judith , Koeleman Bobby P. C. , Ophoff Roel A. , Strengman Eric , van Elburg Annemarie A. , Bruson Alice , Clementi Maurizio , Degortes Daniela , Forzan Monica , Tenconi Elena , Docampo Elisa , Escaramís Geòrgia , Jiménez-Murcia Susana , Lissowska Jolanta , Rajewski Andrzej , Szeszenia-Dabrowska Neonila , Slopien Agnieszka , Hauser Joanna , Karhunen Leila , Meulenbelt Ingrid , Slagboom P. Eline , Tortorella Alfonso , Maj Mario , Dedoussis George , Dikeos Dimitris , Gonidakis Fragiskos , Tziouvas Konstantinos , Tsitsika Artemis , Papezova Hana , Slachtova Lenka , Martaskova Debora , Kennedy James L. , Levitan Robert D. , Yilmaz Zeynep , Huemer Julia , Koubek Doris , Merl Elisabeth , Wagner Gudrun , Lichtenstein Paul , Breen Gerome , Cohen-Woods Sarah , Farmer Anne , McGuffin Peter , Cichon Sven , Giegling Ina , Herms Stefan , Dan Rujescu  , Schreiber Stefan , Wichmann H-Erich , Dina Christian , Sladek Rob , Gambaro Giovanni , Soranzo Nicole , Julia Antonio , Marsal Sara , Rabionet Raquel , Gaborieau Valerie , Dick Danielle M. , Palotie Aarno , Ripatti Samuli , Widén Elisabeth , Andreassen Ole A. , Espeseth Thomas , Lundervold Astri , Reinvang Ivar , Steen Vidar M. , Le Hellard Stephanie , Mattingsdal Morten , Ntalla Ioanna , Bencko Vladimir , Foretova Lenka , Janout Vladimir , Navratilova Marie , Gallinger Steven , Pinto Dalila , Scherer Stephen W. , Aschauer Harald , Carlberg Laura , Schosser Alexandra , Alfredsson Lars , Ding Bo , Klareskog Lars , Padyukov Leonid , Finan Chris , Kalsi Gursharan , Roberts Marion , Barrett Jeff C. , Estivill Xavier , Hinney Anke , Sullivan Patrick F. , Zeggini Eleftheria , Bulik Cynthia M. ,   Price Foundation Collaborative Group, Brandt Harry , Crawford Steve , Crow Scott , Fichter Manfred M. , Halmi Katherine A. , Johnson Craig , Kaplan Allan S. , La Via Maria C. , Mitchell James , Strober Michael , Rotondo Alessandro , Treasure Janet , Woodside D. Blake , Bulik Cynthia M. , Keel Pamela K. , Klump Kelly L. , Lilenfeld Lisa , Thornton Laura M. , Bergen Andrew W. , Berrettini Wade , Kaye Walter , Magistretti Pierre , Hakonarson Hakon 
Published: June 2017

We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10−7; OR = 0.7; 95% confidence interval (CI) = 0.61–0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.