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

Melissa Munn-Chernoff 1, 2 Emma Johnson 3 Yi-Ling Chou 3 Jonathan R.I. Coleman 4 Laura Thornton 2, 1 Raymond Walters 5, 6 Zeynep Yilmaz 2 Jessica Baker 2 Christopher Hübel 1, 4 Scott Gordon 7 Sarah Medland 7 Hunna Watson 2 Héléna Gaspar 4 Julien Bryois 8 Anke Hinney 9, 10 Virpi Leppä 8 Manuel Mattheisen 11, 8, 12, 13 Stephan Ripke 6, 5 Shuyang Yao 8 Paola Giusti-Rodríguez 1 Ken Hanscombe 14, 15 Roger A.H. Adan 16, 17, 18 Lars Alfredsson 8 Tetsuya Ando 19 Ole Andreassen 20, 21 Wade Berrettini 22, 23 Ilka Boehm 24 Claudette Boni 25 Vesna Boraska Perica 26, 27 Katharina Buehren 28 Roland Burghardt 29 Matteo Cassina 30 Sven Cichon 31, 32 Maurizio Clementi 30 Roger Cone 33 Philippe Courtet 34 Scott Crow 35 James Crowley 1 Unna Danner 18 Oliver S.P. Davis 36 Martina de Zwaan 37 George Dedoussis 38 Daniela Degortes 30 Janiece Desocio 39 Danielle Dick 40 Dimitris Dikeos 41 Christian Dina 42 Monika Dmitrzak-Weglarz 43 Elisa Docampo 44 Laramie Duncan 45 Karin Egberts 46 Stefan Ehrlich 47 Geòrgia Escaramís 44 Tõnu Esko 48 Xavier Estivill 49 Anne Farmer 50 Angela Favaro 30 Fernando Fernández-Aranda 51 Manfred Fichter 52 Krista Fischer 53 Manuel Föcker 54 Lenka Foretova 55 Andreas Forstner 56 Monica Forzan 30 Christopher Franklin 27 Steven Gallinger 57 Ina Giegling 58 Johanna Giuranna 59 Fragiskos Gonidakis 60 Philip Gorwood 25 Monica Gratacos Mayora 44 Sébastien Guillaume 34 Yiran Guo 61 Hakon Hakonarson 62 Konstantinos Hatzikotoulas 27 Joanna Hauser 63 Johannes Hebebrand 64 Sietske Helder 14, 4 Stefan Herms 65 Beate Herpertz-Dahlmann 66 Wolfgang Herzog 67 Laura Huckins 68 James Hudson 69 Hartmut Imgart 70 Hidetoshi Inoko 71 Vladimír Janout 72 Susana Jiménez-Murcia 51 Antonio Julià 73 Gursharan Kalsi 4 Deborah Kaminská 74 Leila Karhunen 75 Andreas Karwautz 76 Martien J.H. Kas 16 James Kennedy 77 Anna Keski-Rahkonen 78 Kirsty Kiezebrink 79 Youl-Ri Kim 80 Kelly Klump 81 Gun Peggy S. Knudsen 82 Maria La Via 1 Stephanie Le Hellard 83 Robert Levitan 77 Dong Li 84 Lisa Lilenfeld 85 Bochao Danae Lin 16 Jolanta Lissowska 86 Jurjen Luykx 16 Pierre Magistretti 87 Mario Maj 88 Katrin Männik 89 Sara Marsal 73 Christian Marshall 90 Morten Mattingsdal 91 Sara Mcdevitt 92 Peter Mcguffin 50 Andres Metspalu 48 Ingrid Meulenbelt 93 Nadia Micali 94 Karen Mitchell 95 Alessio Maria Monteleone 96 Palmiero Monteleone 88 Benedetta Nacmias 97 Marie Navratilova 98 Ioanna Ntalla 38 Julie O'Toole 99 Roel Ophoff 100 Leonid Padyukov 8 Aarno Palotie 101 Jacques Pantel 102 Hana Papezova 74 Dalila Pinto 103 Raquel Rabionet 104 Anu Raevuori 78 Nicolas Ramoz 25 Ted Reichborn-Kjennerud 82 Valdo Ricca 97 Samuli Ripatti 105 Franziska Ritschel 24 Marion Roberts 4 Alessandro Rotondo 106 Dan Rujescu 107 Filip Rybakowski 43 Paolo Santonastaso 30 Andre Scherag 108 Stephen Scherer 90 Ulrike Schmidt 4 Nicholas Schork 109 Alexandra Schosser 110 Jochen Seitz 28 Lenka Slachtova 74 P. Eline Slagboom 111 Margarita C.T. Slof-Op'T Landt 112 Agnieszka Slopien 43 Sandro Sorbi 97 Beata Świątkowska 113 Jin Szatkiewicz 114 Ioanna Tachmazidou 27 Elena Tenconi 30 Alfonso Tortorella 88 Federica Tozzi 115 Janet Treasure 4 Artemis Tsitsika 60 Marta Tyszkiewicz-Nwafor 43 Konstantinos Tziouvas 60 Annemarie van Elburg 116 Eric van Furth 112 Gudrun Wagner 117 Esther Walton 118 Elisabeth Widén 58 Eleftheria Zeggini 119 Stephanie Zerwas 1 Stephan Zipfel 120 Andrew Bergen 121 Joseph Boden 122 Harry Brandt 123 Steven Crawford 123 Katherine Halmi 124 L. John Horwood 122 Craig Johnson 125 Allan Kaplan 126 James Mitchell Walter Kaye 127 Catherine Olsen 7 John Pearson 128 Nancy Pedersen 105 Michael Strober 129 Thomas Werge 130 David Whiteman 7 D. Blake Woodside 131 Jakob Grove 11 Anjali Henders 132 Janne Larsen 133 Richard Parker 7 Liselotte Petersen 134 Jennifer Jordan 122 Martin Kennedy 122 Andreas Birgegård 12 Paul Lichtenstein 8 Claes Norring 12 Mikael Landén 135 Preben Bo Mortensen 136 Renato Polimanti 137 Jeanette Mcclintick 138 Amy Adkins 40 Fazil Aliev 40 Silviu-Alin Bacanu 40 Anthony Batzler 139 Sarah Bertelsen 68 Joanna Biernacka 140 Tim Bigdeli 141 Li-Shiun Chen 3 Toni-Kim Clarke 142 Franziska Degenhardt 143 Anna Docherty 144 Alexis Edwards 40 Jerome Foo 145 Louis Fox 3 Josef Frank 146 Laura Hack 46 Annette Hartmann 136 Sarah Hartz 3 Stefanie Heilmann-Heimbach 147 Colin Hodgkinson 148, 149 Per Hoffmann 150 Jouke-Jan Hottenga 58 Bettina Konte 151 Jari Lahti 78 Marius Lahti-Pulkkinen 78 Dongbing Lai 138 Lannie Ligthart 58 Anu Loukola 152 Brion Maher 153 Hamdi Mbarek 154 Andrew Mcintosh 155 Matthew Mcqueen 156 Jacquelyn Meyers 152 Yuri Milaneschi 157 Teemu Palviainen 40 Roseann Peterson 139 Euijung Ryu 3 Nancy Saccone 40 Jessica Salvatore 127 Sandra Sanchez-Roige 148, 149 Melanie Schwandt 158 Richard Sherva 40 Fabian Streit 159 Jana Strohmaier 160 Nathaniel Thomas 68 Jen-Chyong Wang 40 Bradley Webb 161 Robbee Wedow 138 Leah Wetherill 162 Amanda Wills 156 Hang Zhou Jason Boardman 6 Danfeng Chen 139 Doo-Sup Choi 163 William Copeland 3 Robert Culverhouse 164 Norbert Dahmen 14 Louisa Degenhardt 46 Benjamin Domingue 165 Mark Frye 140 Wolfgang Gäbel 35 Caroline Hayward 166 Marcus Ising 167 Margaret Keyes 168 Falk Kiefer 169 Gabriele Koller 170 John Kramer 14 Samuel Kuperman 169 Susanne Lucae 171 Michael Lynskey 79 Wolfgang Maier 172 Karl Mann 145 Satu Männistö 173 Bertram Müller-Myhsok 174 Alison Murray 151 John Nurnberger 175 Ulrich Preuss 176 Katri Räikkönen 58 Maureen Reynolds 177 Monika Ridinger 10 Norbert Scherbaum 127 Marc Schuckit 52 Michael Soyka 177 Jens Treutlein 178 Stephanie Witt 159 Norbert Wodarz 52 Peter Zill 179 Daniel Adkins 127 Dorret Boomsma 58 Laura Bierut 180 Sandra Brown 3 Kathleen Bucholz 181 E. Jane Costello 182 Harriet de Wit 149 Nancy Diazgranados 40 Johan Eriksson 58 Lindsay Farrer 158 Tatiana Foroud 183 Nathan Gillespie 1 Alison Goate 184 David Goldman 185 Richard Grucza 58 Dana Hancock 186 Kathleen Mullan Harris 187 Victor Hesselbrock 156 John Hewitt 188 Christian Hopfer 35 William Iacono 35 Eric Johnson 189 Victor Karpyak 139 Kenneth Kendler 40 Henry Kranzler 23 Kenneth Krauter 156 Penelope Lind 7 Matt Mcgue 35 James Mackillop 190 Pamela A.F. Madden 3 Hermine Maes 40 Patrik K.E. Magnusson 8 Elliot Nelson 3 Markus Nöthen 150 Abraham Palmer 127 Brenda W.J.H. Penninx 191 Bernice Porjesz 192 John Rice 193 Marcella Rietschel 136 Brien Riley 107 Richard Rose 194 Pei-Hong Shen 148 Judy Silberg 40 Michael Stallings 156 Ralph Tarter 176 Michael Vanyukov 176 Scott Vrieze 35 Tamara Wall 127 John Whitfield 7 Hongyu Zhao 195 Benjamin Neale 196 Tracey Wade 197 Andrew Heath 3 Grant Montgomery 58 Nicholas Martin 198 Patrick Sullivan 8 Jaakko Kaprio 199 Gerome Breen 50 Joel Gelernter 200 Howard Edenberg 201 Cynthia Bulik 1 Arpana Agrawal 58
21 NORMENT - Norwegian Centre for Mental Disorders Research [Oslo]
UiO - University of Oslo, Haukeland University Hospital, Oslo University Hospital [Oslo]
117 SURFACES
IRCELYON - Institut de recherches sur la catalyse et l'environnement de Lyon
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 [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.
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Melissa Munn-Chernoff, Emma Johnson, Yi-Ling Chou, Jonathan R.I. Coleman, Laura Thornton, et al.. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies. Addiction Biology, Wiley, 2020, 40, pp.e12880. ⟨10.1111/adb.12880⟩. ⟨inserm-02881410⟩

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