Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies.
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 [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 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 (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 nondiagnostic 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 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.
Authors
- Allan S. Kaplan (ORCID: https://orcid.org/0000-0001-5077-2787)
- Stefan Ehrlich (ORCID: https://orcid.org/0000-0003-2132-4445)
- Jessica E. Salvatore (ORCID: https://orcid.org/0000-0001-5504-5087)
- Hartmut Imgart (ORCID: https://orcid.org/0000-0002-3997-0376)
- Beata Świątkowska (ORCID: https://orcid.org/0000-0003-3757-3868)
- André Scherag (ORCID: https://orcid.org/0000-0002-9406-4704)
- Jolanta Lissowska (ORCID: https://orcid.org/0000-0003-2695-5799)
- Joanna Hauser (ORCID: https://orcid.org/0000-0002-6621-3493)
- Jaakko A. Kaprio (ORCID: https://orcid.org/0000-0002-3716-2455)
- Nancy Diazgranados (ORCID: https://orcid.org/0000-0002-7415-8455)
- Marius Lahti‐Pulkkinen (ORCID: https://orcid.org/0000-0002-5244-5525)
- Tim B. Bigdeli (ORCID: https://orcid.org/0000-0003-2215-5946)
- Cynthia Marie Bulik (ORCID: https://orcid.org/0000-0001-7772-3264)
- Ted Reichborn‐Kjennerud (ORCID: https://orcid.org/0000-0003-4653-0034)
- Anke Hinney (ORCID: https://orcid.org/0000-0001-5659-0706)
- Fernando Fernández‐Aranda (ORCID: https://orcid.org/0000-0002-2968-9898)
- Sandra A. Brown (ORCID: https://orcid.org/0000-0001-8780-0323)
- Kirsty Kiezebrink (ORCID: https://orcid.org/0000-0002-9154-426X)
- Penelope A. Lind (ORCID: https://orcid.org/0000-0002-3887-2598)
- Laura M. Huckins (ORCID: https://orcid.org/0000-0002-5369-6502)
- Silviu‐Alin Bacanu (ORCID: https://orcid.org/0000-0002-4364-1583)
- Zeynep Yılmaz (ORCID: https://orcid.org/0000-0002-8145-1596)
- Tōnu Esko (ORCID: https://orcid.org/0000-0003-1982-6569)
- Louisa Degenhardt (ORCID: https://orcid.org/0000-0002-8513-2218)
- Janet Treasure (ORCID: https://orcid.org/0000-0003-0871-4596)
- Sarah Bertelsen (ORCID: https://orcid.org/0000-0002-9498-7963)
- Gudrun Wagner (ORCID: https://orcid.org/0000-0002-4845-9684)
- Raquel Rabionet (ORCID: https://orcid.org/0000-0001-5006-8140)
- Andrew Mark McIntosh (ORCID: https://orcid.org/0000-0002-0198-4588)
- Gerome D. Breen (ORCID: https://orcid.org/0000-0003-2053-1792)
- Monika Ridinger (ORCID: https://orcid.org/0000-0002-5887-3264)
- Karen S. Mitchell (ORCID: https://orcid.org/0000-0002-1516-7239)
- Nicolás Ramoz (ORCID: https://orcid.org/0000-0002-8070-9938)
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- Stéphanie Le Hellard (ORCID: https://orcid.org/0000-0002-8085-051X)
- Virpi Leppä (ORCID: https://orcid.org/0000-0003-2942-2656)
- Amanda G. Wills (ORCID: https://orcid.org/0000-0002-1883-2927)
- Bettina Konte (ORCID: https://orcid.org/0000-0001-5287-308X)
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- HERMINE H. M. MAES (ORCID: https://orcid.org/0000-0001-7489-2214)
- Xavier Estivill (ORCID: https://orcid.org/0000-0002-0723-2256)
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- Robbee Wedow (ORCID: https://orcid.org/0000-0002-3108-7087)
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- Stefan Herms (ORCID: https://orcid.org/0000-0002-2786-8200)
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- Jonathan R. I. Coleman (ORCID: https://orcid.org/0000-0002-6759-0944)
- Richard Sherva (ORCID: https://orcid.org/0000-0003-2133-1493)
- Franziska Degenhardt (ORCID: https://orcid.org/0000-0002-1685-8904)
- Dorret Irene Boomsma (ORCID: https://orcid.org/0000-0002-7099-7972)
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- Claudette Boni
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- Roland Burghardt (ORCID: https://orcid.org/0000-0001-7904-9090)
- Andrew W. Bergen (ORCID: https://orcid.org/0000-0002-1237-7644)
- Paolo Santonastaso (ORCID: https://orcid.org/0000-0002-7408-0563)
- Leah Flury Wetherill (ORCID: https://orcid.org/0000-0003-2888-9051)
- Doo‐Sup Choi (ORCID: https://orcid.org/0000-0002-6796-9938)
- Fabian Streit (ORCID: https://orcid.org/0000-0003-1080-4339)
- Kelly L. Klump (ORCID: https://orcid.org/0000-0003-1790-9264)
- Bradley T. Webb (ORCID: https://orcid.org/0000-0002-0576-5366)
- Liselotte Vogdrup Petersen (ORCID: https://orcid.org/0000-0002-0479-5379)
- Bernice Porjesz (ORCID: https://orcid.org/0000-0003-2489-0389)
- Aarno V. Palotie (ORCID: https://orcid.org/0000-0002-2527-5874)
- Unna N. Danner (ORCID: https://orcid.org/0000-0001-7038-5717)
- Walter H. Kaye (ORCID: https://orcid.org/0000-0002-4478-4906)
- Eric O. Johnson (ORCID: https://orcid.org/0000-0002-8870-1949)
- Alexandra Schosser (ORCID: https://orcid.org/0000-0002-5715-3740)
- Morten Mattingsdal
- Elliot C. Nelson (ORCID: https://orcid.org/0000-0002-3037-3962)
- Håkon Håkonarson (ORCID: https://orcid.org/0000-0003-2814-7461)
- Dalila Pinto (ORCID: https://orcid.org/0000-0002-8769-0846)
- Jens Treutlein (ORCID: https://orcid.org/0000-0003-3952-8905)
- John F. Pearson (ORCID: https://orcid.org/0000-0001-5607-4517)
- Susanne Lucae (ORCID: https://orcid.org/0000-0001-6263-3485)
- Lannie Ligthart (ORCID: https://orcid.org/0000-0002-6570-3319)
- Victor Hesselbrock (ORCID: https://orcid.org/0000-0002-0495-8641)
- Alison Goate (ORCID: https://orcid.org/0000-0002-0576-2472)
- Agnieszka Słopień (ORCID: https://orcid.org/0000-0001-7821-8972)
- Christian J. Hopfer (ORCID: https://orcid.org/0000-0003-3085-3509)
- Marcella Rietschel (ORCID: https://orcid.org/0000-0002-5236-6149)
- Raymond K. Walters (ORCID: https://orcid.org/0000-0001-8422-6530)
- Manuel Mattheisen (ORCID: https://orcid.org/0000-0002-8442-493X)
- Jessica H. Baker (ORCID: https://orcid.org/0000-0002-3997-2398)
- Dong Li (ORCID: https://orcid.org/0000-0002-2265-6727)
- Andrew C. Heath (ORCID: https://orcid.org/0000-0002-9414-6857)
- Michael Soyka
- Ilka Boehm (ORCID: https://orcid.org/0000-0003-0194-7557)
- James MacKillop (ORCID: https://orcid.org/0000-0003-4118-9500)
- Tetsuya Ando (ORCID: https://orcid.org/0000-0003-2643-6067)
- Louis Fox (ORCID: https://orcid.org/0000-0003-0721-7889)
- Alessandro Rotondo
- Julie K. O’Toole
- Mario Maj
- Maurizio Clementi (ORCID: https://orcid.org/0000-0002-1308-8617)
- Konstantinos Tziouvas (ORCID: https://orcid.org/0000-0002-6863-7708)
- Manfred M. Fichter
- Wade H. Berrettini
- Sven Cichon (ORCID: https://orcid.org/0000-0002-9475-086X)
- Michael Strober
- Philippe Courtet
- Martina de Zwaan
- Gun Peggy Knudsen
- Dan Rujescu
- Federica Tozzi
- Eleftheria Zeggini
- Stephanie Zerwas
- George Dedoussis
- Christopher S. Franklin
- Laura M. Thornton
- Danielle M. Dick
- Robert D. Levitan
- Jin P. Szatkiewicz
- Beate Herpertz‐Dahlmann
- Sietske G. Helder
- Geòrgia Escaramís
- Ulrike Schmidt (ORCID: https://orcid.org/0000-0003-1335-1937)
- Filip Rybakowski
- Marion Roberts
- Katrin Männik
- Dimitris Dikeos
- Marie Navratilova
- Elena Tenconi
- Gabriele Koller
- Peter McGuffin
- Ioanna Tachmazidou
- Elisabeth Widén (ORCID: https://orcid.org/0000-0001-7108-2806)
- Margaret A. Keyes
- Janiece E. DeSocio
- Anne Farmer
- Yi‐Ling Chou
- Ingrid Meulenbelt
- Wolfgang Maier
- Fragiskos Gonidakis
Institutions
- University of North Carolina at Chapel Hill (US)
Publication Details
- Journal
- Archive ouverte UNIGE (University of Geneva)
- Published
- 2026-02-10
- DOI
- https://doi.org/10.17615/9jk0-cr18
- Primary Topic
- Eating Disorders and Behaviors
- Type
- article
- Field-Weighted Citation Impact
- 0.00