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

Dong Li, Xiao Chang, John J.M. Connolly, Lifeng Tian, Yichuan Liu, Elizabeth J. Bhoj, Nora Robinson, Debra J. Abrams, Yun R. Li, Jonathan P. Bradfield, Cecilia E. Kim, Jin Li, Fengxiang Wang, James Snyder, Maria Lemma, Cuiping Hou, Zhi Wei, Y. Guo, Haijun Qiu, Frank D. MentchKelly A. Thomas, Rosetta M. Chiavacci, Roger D. Cone, Bingshan Li, Patrick M.A. Sleiman, Håkon H. Håkonarson, Vesna Boraska Perica, Christopher S. Franklin, James A.B. Floyd, Laura Marie Thornton, Laura M. Huckins, Lorraine Southam, Nigel William Rayner, Ioanna Tachmazidou, Ulrike H. Schmidt, Federica Tozzi, Kirsty Kiezebrink, Johannes Hebebrand, Philip A.P.M. Gorwood, Roger A.H. Adan, Martien J.H. Kas, Angela Favaro, Paolo Santonastaso, Fernando Fernánde-Aranda, Mònica Gratacòs, Filip Rybakowski, Monika Paulina 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 Knudsen, Palmiero Monteleone, Andreas F.K. Karwautz, Wade H. Berrettini, Nicholas J. Schork, Tetsuya Ando, Hidetoshi Inoko, Tõnu Esko, Krista Fischer, Katrin Männik, Andres Metspalu, Jessica H. Baker, Janiece E. DeSocio, Christopher E. Hilliard, Julie K. O'Toole, Jacques Pantel, Jin Peng Szatkiewicz, Stephanie C. Zerwas, Oliver S.P. Davis, Sietske G. Helder, Katharina Bühren, Roland Burghardt, Martina De Zwaan, Karin Maria Egberts, Stefan Ehrlich, Beate M. 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, R. A. Ophoff, Eric Strengman, Annemarie A. Van Elburg, Alice Bruson, Maurizio Clementi, Daniela Degortes, Monica Forzan, Elena Tenconi, Elisa Docampo, Georgia Escaramis, Susana Jiménez-Múrcia, Jolanta Lissowska, Andrzej Rajewski -, Neonila Szeszenia-Da¸browska, Agnieszka Slopien, Joanna Wiktoria Hauser, Leila J. Karhunen, Ingrid M. Meulenbelt, Pieternella Eline Slagboom, Alfonso Tortorella, Mario Maj, George V.Z. Dedoussis, Dimitris G. Dikeos, Fragiskos Gonidakis, K. Tziouvas, Artemis Tsitsika, Hana Papezová, Lenka Šlachtová, D. Martásková, James Lowery Kennedy, Robert Daniel Levitan, Zeynep Yilmaz, Julia Huemer, Doris Koubek, Elisabeth Merl, Gudrun Wagner, Paul Lichtenstein, Gerome Breen, Sarah Louise Cohen-Woods, Anne E. Farmer, Peter McGuffin, Sven Cichon, Ina Giegling, Stefan Herms, Dan Rujescu, Stefan Schreiber, Heinz Erich Wichmann, Christian Dina, Robert S. Sladek, Giovanni Gambaro, Nicole Soranzo, Antonio F. Julià, Sara Marsal, Raquel Rabionet, Valérie Gaborieau, Danielle M. Dick, Aarno V. Palotie, Samuli O. Ripatti, Elisabeth E. Widén, Ole Andreas Andreassen, Thomas Espeseth, Astri Johansen Lundervold, Ivar R. Reinvang, Vidar Martin Steen, Stéphanie Le Hellard, Morten Mattingsdal, Ioanna Ntalla, Vladimir Bencko, Lenka Foretová, Vladimír Janout, Marie Navrátilová, Steven J. Gallinger, Dalila Pinto, Stephen W. Scherer, Harald Nikolaus Aschauer, Laura Carlberg, Alexandra Schosser, Lars S. Alfredsson, Bo Ding, Lars G. Klareskog, Leonid Padyukov, Chris I. Finan, Gursharan K. Kalsi, Marion E. Roberts, Jeffrey C. Barrett, Xavier Estivill, Anke Hinney, Patrick F. Sullivan, Eleftheria Zeggini, Cynthia Marie Bulik, Harry A. Brandt, Steve F. Crawford, Scott J. Crow, Manfred Maximilian Fichter, Katherine Ann Halmi., Craig L. Johnson, Allan S. Kaplan, Maria C. la Via, James E. Mitchell, Michael A. Strober, Alessandro Rotondo, Janet Treasure, D. Blake Woodside, Pamela K. Keel, Kelly L. Klump, Lisa Rachelle Lilenfeld, Andrew W. Bergen, Walter H. Kaye, Pierre J. Magistretti

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9 Citations (Scopus)

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
Article number3847
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017

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    Li, D., Chang, X., Connolly, J. J. M., Tian, L., Liu, Y., Bhoj, E. J., Robinson, N., Abrams, D. J., Li, Y. R., Bradfield, J. P., Kim, C. E., Li, J., Wang, F., Snyder, J., Lemma, M., Hou, C., Wei, Z., Guo, Y., Qiu, H., ... Magistretti, P. J. (2017). A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling. Scientific Reports, 7(1), [3847]. https://doi.org/10.1038/s41598-017-01674-8