Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies.

Authors:
Melissa A Munn-Chernoff Emma C Johnson Yi-Ling Chou Jonathan R I Coleman Laura M Thornton Raymond K Walters Zeynep Yilmaz Jessica H Baker Christopher Hübel Scott Gordon Sarah E Medland Hunna J Watson Héléna A Gaspar Julien Bryois Anke Hinney Virpi M 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 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-Weglarz 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 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 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 L 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 J 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 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 Nicholas J Schork 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 Widen Eleftheria Zeggini Stephanie Zerwas Stephan Zipfel Andrew W Bergen Joseph M Boden Harry Brandt Steven Crawford Katherine A Halmi L John Horwood 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 Toni-Kim Clarke Franziska Degenhardt Anna R Docherty Alexis C Edwards Jerome C Foo Louis Fox Josef Frank Laura M Hack Annette M Hartmann Sarah M 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 S Maher Hamdi Mbarek Andrew M 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 Richard Sherva Fabian Streit Jana Strohmaier Nathaniel Thomas Jen-Chyong Wang Bradley T Webb Robbee Wedow Leah Wetherill Amanda G Wills Hang Zhou Jason D Boardman Danfeng Chen Doo-Sup Choi William E Copeland Robert C Culverhouse Norbert Dahmen Louisa Degenhardt Benjamin W Domingue Mark A Frye Wolfgang Gäebel Caroline Hayward Marcus Ising Margaret Keyes Falk Kiefer Gabriele Koller John Kramer Samuel Kuperman Susanne Lucae Michael T Lynskey Wolfgang Maier Karl Mann Satu Männistö Bertram Müller-Myhsok Alison D Murray John I Nurnberger Ulrich Preuss Katri Räikkönen Maureen D Reynolds Monika Ridinger Norbert Scherbaum Marc A Schuckit Michael Soyka Jens Treutlein Stephanie H 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 A Farrer Tatiana M Foroud Nathan A Gillespie Alison M Goate David Goldman Richard A Grucza Dana B Hancock Kathleen Mullan Harris Victor Hesselbrock John K Hewitt Christian J Hopfer William G Iacono Eric O Johnson Victor M Karpyak Kenneth S 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 Nöthen Abraham A Palmer Brenda W J H 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 Gerome Breen Joel Gelernter Howard J Edenberg Cynthia M Bulik Arpana Agrawal

Addict Biol 2020 Feb 16:e12880. Epub 2020 Feb 16.

Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, USA.

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 ], 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 = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r = 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 = -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.

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http://dx.doi.org/10.1111/adb.12880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429266PMC
February 2020

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