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Shared Genetic Risk between Eating Disorder- and Substance-Use-Related Phenotypes: Evidence from Genome-Wide Association Studies

By Melissa A Munn-Chernoff, Emma C Johnson, Yi-Ling Chou, Jonathan RI Coleman, Laura M. Thornton, Raymond K Walters, Zeynep Yilmaz, Jessica H Baker, Christopher Hubel, Scott Gordon, Sarah E. Medland, Hunna J. Watson, Héléna A. Gaspar, Julien Bryois, Anke Hinney, Virpi M. Leppä, Manuel Mattheisen, Stephan Ripke, Paola Giusti-Rodríguez, Ken B Hanscombe, Roger A.H. Adan, Lars Alfredsson, Tetsuya Ando, Ole Andreassen, Wade H Berrettini, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Matteo Cassina, Sven Cichon, Maurizio Clementi, Roger D. Cone, Philippe Courtet, Scott Crow, James J Crowley, Unna N. Danner, Oliver S.P Davis, Martina de Zwaan, George V. Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M Dick, Dimitris Dikeos, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo, Laramie E Duncan, Karin Egberts, Stefan Ehrlich, Geòrgia Escaramís, Tõnu Esko, Xavier Estivil, Anne Farmer, Angela Favaro, Fernando Fernández-Aranda, Manfred M. Fichter, Krista Fischer, Manuel Föcker, Lenka Foretova, Andreas J. Forstner, Monica Forzan, Christopher S. Franklin, Steven Gallinger, Ina Giegling, Johanna Giuranna, Fragiskos Gonidakis, Philip Gorwood, Monica Gratacos Mayora, Sébastien Guillaume, Yiran Guo, Hakon Hakonarson, Konstantinos Hatzikotoulas, Joanna Twarowska-Hauser, Johannes Hebebrand, Sietske G. Helder, Stefan Herms, Beate Herpertz-Dahlmann, Wolfgang Herzog, Laura M Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Susana Jiménez-Murcia, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Leila Karhunen, Andreas Karwautz, Martien J.H. Kas, James Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Kelly L Klump, Gun Peggy S Knudsen, Maria C. La Via, Stephanie Le Hellard, Robert D. Levitan, Dong Li, Lisa Lilenfeld, Bochao Danae Lin, Jolanta Lissowska, Jurjen Luykx, Pierre Julius Magistretti, Mario Maj, Katrin Mannik, Sara Marsal, Christian R. Marshall, Morten Mattingsdal, Sara McDevitt, Peter McGuffin, Andres Metspalu, Ingrid Meulenbelt, Nadia Micali, Karen Mitchell, Alessio Maria Monteleone, Palmiero Monteleone, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Roel A Ophoff, Leonid Padyukov, Aarno G. Palotie, Jacques Pantel, Hana Papezova, Dalila Pinto, Raquel Rabionet, Anu Raevuori, Nicolas Ramoz, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Alessandro Rotondo, Dan Rujescu, Filip Rybakowski, Paolo Santonastaso, André Scherag, Stephen W Scherer, Ulrike Schmidt, Ali Torkamani, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P. Eline Slagboom, Margarita C.T. Slof-Op’t Landt, Agnieszka Slopien, Sandro Sorbi, Beata Świątkowska, Jin P Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Janet Treasure, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Gudrun Wagner, Esther Walton, Elisabeth Widén, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Andrew Wells Bergen, Joseph M. Boden, Harry Brandt, Steven Crawford, Katherine A Halmi, John Horwood, W. Craig Johnson, Allan S. Kaplan, Walter H. Kaye, James Mitchell, Catherine M. Olsen, John F. Pearson, Nancy L. Pedersen, Michael Strober, Thomas Werge, David C. Whiteman, D. Blake Woodside, Jakob Grove, Anjali K. Henders, Janne T. Larsen, Richard Parker, Liselotte V. Petersen, Jennifer Jordan, Martin A Kennedy, Andreas Birgegård, Paul Lichtenstein, Claes Norring, Mikael Landén, Preben Bo Mortensen, Renato Polimanti, Jeanette N. McClintick, Amy E. Adkins, Fazil Aliev, Silviu-Alin Bacanu, Anthony Batzler, Sarah Bertelsen, Joanna M Biernacka, Tim B. Bigdeli, Li-Shiun Chen, T-K Clarke, Franziska Degenhardt, Anna R. Docherty, Alexis C Edwards, Jerome C Foo, Louis Fox, Josef Frank, Laura M Hack, Annette M Hartmann, Sarah Hartz, Stefanie Heilmann-Heimbach, Colin Hodgkinson, Per Hoffmann, Jouke-Jan Hottenga, Bettina Konte, Jari Lahti, Marius Lahti-Pulkkinen, Dongbing Lai, lannie ligthart, Anu Loukola, Brion Maher, Hamdi Mbarek, Andrew McIntosh, Matthew B McQueen, Jacquelyn L Meyers, Yuri Milaneschi, Teemu Palviainen, Roseann E Peterson, Euijung Ryu, Nancy L Saccone, Jessica E. Salvatore, Sandra Sanchez-Roige, Melanie Schwandt, Joel Gelernter, Fabian Streit, Jana Strohmaier, Nathaniel Thomas, Jen-Chyong Wang, Bradley Todd Webb, Robbee Wedow, Leah Wetherill, Amanda G. Wills, Hang Zhou, Jason D. Boardman, Danfeng Chen, Doo-Sup Choi, William L. Copeland, Robert C. Culverhouse, Norbert Dahmen, Louisa Degenhardt, Benjamin W. Domingue, Mark A. Frye, Wolfgang Gäbel, Caroline Hayward, Marcus Ising, Margaret Keyes, Falk Kiefer, Gabrielle Koller, John R Kramer, Samuel Kuperman, Susanne Lucae, Michael Lynskey, Wolfgang Maier, Karl Mann, Satu Männistö, Bertram Mueller-Myhsok, Alison Murray, John I. Nurnberger, Ulrich Preuss, Katri Raikkonen, Maureen D. Reynolds, Monika Ridinger, Norbert Scherbaum, Marc A. Schuckit, Michael Soyka, Jens Treutlein, Stephanie Witt, Norbert Wodarz, Peter Zill, Daniel E Adkins, Dorret I Boomsma, Laura J Bierut, Sandra A. Brown, Kathleen K Bucholz, E. Jane Costello, Harriet de Wit, Nancy Diazgranados, Johan G. Eriksson, Lindsay Farrer, Tatiana M. Foroud, Nathan A. Gillespie, Alison M Goate, David Goldman, Richard A. Grucza, Dana B Hancock, Kathleen M Harris, Victor Hesselbrock, John Hewitt, Christian J. Hopfer, William G Iacono, Eric O Johnson, Victor M. Karpyak, Kenneth Kendler, Henry R. Kranzler, Kenneth Krauter, Penelope A. Lind, Matt McGue, James MacKillop, Pamela A.F. Madden, Hermine H Maes, Patrik K.E. Magnusson, Elliot C Nelson, Markus M Nothen, Abraham A. Palmer, Brenda WJH Penninx, Bernice Porjesz, John P. Rice, Marcella Rietschel, Brien P Riley, Richard J Rose, Pei-Hong Shen, Judy Silberg, Michael C. Stallings, Ralph E. Tarter, Michael M. Vanyukov, Scott Vrieze, Tamara L. Wall, John B Whitfield, Hongyu Zhao, Benjamin M Neale, Tracey D Wade, Andrew C. Heath, Grant W Montgomery, Nicholas G Martin, Patrick F Sullivan, Jaakko Kaprio, Inti Pedroso, Joel Gelernter, Howard J Edenberg, Cynthia Bulik, Arpana Agrawal

Posted 23 Aug 2019
bioRxiv DOI: 10.1101/741512 (published DOI: 10.1111/adb.12880)

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; q<0.0001), and cannabis initiation and AN with binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to -0.23; qs<0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for MDD loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships between these behaviors.

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