A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number3847
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General

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