Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies
Melissa A. Munn‐Chernoff, Emma C. Johnson, Yi‐Ling Chou, Jonathan R. I. Coleman, Laura M. Thornton, Raymond K. Walters, Zeynep Yılmaz, Jessica H. Baker, Christopher Hübel, Scott D. Gordon, Sarah E. Medland, Hunna J. Watson, Héléna A. Gaspar, Julien Bryois, Anke Hinney, Virpi Leppä, Manuel Mattheisen, Stephan Ripke, Shuyang Yao, Paola Giusti‐Rodríguez, Ken B. Hanscombe, Roger A.H. Adan, Lars Alfredsson, Tetsuya Ando, Ole A. 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 J. Crow, James J. Crowley, Unna N. Danner, Oliver S. P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Dimitris Dikeos, Christian Dina, Monika Dmitrzak‐Węglarz, Elisa Docampo, Laramie E. Duncan, Karin Egberts, Stefan Ehrlich, Geòrgia Escaramís, Tõnu Esko, Xavier Estivill, Anne Farmer, Angela Favaro, Fernando Fernández‐Aranda, Manfred M. Fichter, Krista Fischer, Manuel Föcker, Lenka Foretová, 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, Håkon Håkonarson, Konstantinos Hatzikotoulas, Joanna Hauser, Johannes Hebebrand, Sietske G. Helder, Stefan Herms, Beate Herpertz‐Dahlmann, Wolfgang Herzog, Laura M. Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimír Janout, Susana Jiménez‐Múrcia, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Leila Karhunen, Andreas Karwautz, Martien J. Kas, James L. Kennedy, Anna Keski‐Rahkonen, Kirsty Kiezebrink, Youl‐Ri Kim, Kelly L. Klump, Gun Peggy Knudsen, Maria C. La Via
Abstract
Abstract 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 and problem alcohol use (genetic correlation [ r g ], 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 bulimia nervosa 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 and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 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 ( r g = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN ( r g = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating ( r g = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating ( r gs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co‐varying for major depressive disorder loci. The patterns of association between eating disorder‐ and substance‐use‐related phenotypes highlights the potentially complex and substance‐specific relationships among these behaviors.