@article{3020596,
    title = "Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies",
    author = "Munn-Chernoff, M.A. and Johnson, E.C. and Chou, Y.-L. and Coleman, J.R.I. and Thornton, L.M. and Walters, R.K. and Yilmaz, Z. and Baker, J.H. and Hübel, C. and Gordon, S. and Medland, S.E. and Watson, H.J. and Gaspar, H.A. and Bryois, J. and Hinney, A. and Leppä, V.M. and Mattheisen, M. and Ripke, S. and Yao, S. and Giusti-Rodríguez, P. and Hanscombe, K.B. and Adan, R.A.H. and Alfredsson, L. and Ando, T. and Andreassen, O.A. and Berrettini, W.H. and Boehm, I. and Boni, C. and Boraska Perica, V. and Buehren, K. and Burghardt, R. and Cassina, M. and Cichon, S. and Clementi, M. and Cone, R.D. and Courtet, P. and Crow, S. and Crowley, J.J. and Danner, U.N. and Davis, O.S.P. and de Zwaan, M. and Dedoussis, G. and Degortes, D. and DeSocio, J.E. and Dick, D.M. and Dikeos, D. and Dina, C. and Dmitrzak-Weglarz, M. and Docampo, E. and Duncan, L.E. and Egberts, K. and Ehrlich, S. and Escaramís, G. and Esko, T. and Estivill, X. and Farmer, A. and Favaro, A. and Fernández-Aranda, F. and Fichter, M.M. and Fischer, K. and Föcker, M. and Foretova, L. and Forstner, A.J. and Forzan, M. and Franklin, C.S. and Gallinger, S. and Giegling, I. and Giuranna, J. and Gonidakis, F. and Gorwood, P. and Gratacos Mayora, M. and Guillaume, S. and Guo, Y. and Hakonarson, H. and Hatzikotoulas, K. and Hauser, J. and Hebebrand, J. and Helder, S.G. and Herms, S. and Herpertz-Dahlmann, B. and Herzog, W. and Huckins, L.M. and Hudson, J.I. and Imgart, H. and Inoko, H. and Janout, V. and Jiménez-Murcia, S. and Julià, A. and Kalsi, G. and Kaminská, D. and Karhunen, L. and Karwautz, A. and Kas, M.J.H. and Kennedy, J.L. and Keski-Rahkonen, A. and Kiezebrink, K. and Kim, Y.-R. and Klump, K.L. and Knudsen, G.P.S. and La Via, M.C. and Le Hellard, S. and Levitan, R.D. and Li, D. and Lilenfeld, L. and Lin, B.D. and Lissowska, J. and Luykx, J. and Magistretti, P.J. and Maj, M. and Mannik, K. and Marsal, S. and Marshall, C.R. and Mattingsdal, M. and McDevitt, S. and McGuffin, P. and Metspalu, A. and Meulenbelt, I. and Micali, N. and Mitchell, K. and Monteleone, A.M. and Monteleone, P. and Nacmias, B. and Navratilova, M. and Ntalla, I. and O'Toole, J.K. and Ophoff, R.A. and Padyukov, L. and Palotie, A. and Pantel, J. and Papezova, H. and Pinto, D. and Rabionet, R. and Raevuori, A. and Ramoz, N. and Reichborn-Kjennerud, T. and Ricca, V. and Ripatti, S. and Ritschel, F. and Roberts, M. and Rotondo, A. and Rujescu, D. and Rybakowski, F. and Santonastaso, P. and Scherag, A. and Scherer, S.W. and Schmidt, U. and Schork, N.J. and Schosser, A. and Seitz, J. and Slachtova, L. and Slagboom, P.E. and Slof-Op't Landt, M.C.T. and Slopien, A. and Sorbi, S. and Świątkowska, B. and Szatkiewicz, J.P. and Tachmazidou, I. and Tenconi, E. and Tortorella, A. and Tozzi, F. and Treasure, J. and Tsitsika, A. and Tyszkiewicz-Nwafor, M. and Tziouvas, K. and van Elburg, A.A. and van Furth, E.F. and Wagner, G. and Walton, E. and Widen, E. and Zeggini, E. and Zerwas, S. and Zipfel, S. and Bergen, A.W. and Boden, J.M. and Brandt, H. and Crawford, S. and Halmi, K.A. and Horwood, L.J. and Johnson, C. and Kaplan, A.S. and Kaye, W.H. and Mitchell, J. and Olsen, C.M. and Pearson, J.F. and Pedersen, N.L. and Strober, M. and Werge, T. and Whiteman, D.C. and Woodside, D.B. and Grove, J. and Henders, A.K. and Larsen, J.T. and Parker, R. and Petersen, L.V. and Jordan, J. and Kennedy, M.A. and Birgegård, A. and Lichtenstein, P. and Norring, C. and Landén, M. and Mortensen, P.B. and Polimanti, R. and McClintick, J.N. and Adkins, A.E. and Aliev, F. and Bacanu, S.-A. and Batzler, A. and Bertelsen, S. and Biernacka, J.M. and Bigdeli, T.B. and Chen, L.-S. and Clarke, T.-K. and Degenhardt, F. and Docherty, A.R. and Edwards, A.C. and Foo, J.C. and Fox, L. and Frank, J. and Hack, L.M. and Hartmann, A.M. and Hartz, S.M. and Heilmann-Heimbach, S. and Hodgkinson, C. and Hoffmann, P. and Hottenga, J.-J. and Konte, B. and Lahti, J. and Lahti-Pulkkinen, M. and Lai, D. and Ligthart, L. and Loukola, A. and Maher, B.S. and Mbarek, H. and McIntosh, A.M. and McQueen, M.B. and Meyers, J.L. and Milaneschi, Y. and Palviainen, T. and Peterson, R.E. and Ryu, E. and Saccone, N.L. and Salvatore, J.E. and Sanchez-Roige, S. and Schwandt, M. and Sherva, R. and Streit, F. and Strohmaier, J. and Thomas, N. and Wang, J.-C. and Webb, B.T. and Wedow, R. and Wetherill, L. and Wills, A.G. and Zhou, H. and Boardman, J.D. and Chen, D. and Choi, D.-S. and Copeland, W.E. and Culverhouse, R.C. and Dahmen, N. and Degenhardt, L. and Domingue, B.W. and Frye, M.A. and Gäebel, W. and Hayward, C. and Ising, M. and Keyes, M. and Kiefer, F. and Koller, G. and Kramer, J. and Kuperman, S. and Lucae, S. and Lynskey, M.T. and Maier, W. and Mann, K. and Männistö, S. and Müller-Myhsok, B. and Murray, A.D. and Nurnberger, J.I. and Preuss, U. and Räikkönen, K. and Reynolds, M.D. and Ridinger, M. and Scherbaum, N. and Schuckit, M.A. and Soyka, M. and Treutlein, J. and Witt, S.H. and Wodarz, N. and Zill, P. and Adkins, D.E. and Boomsma, D.I. and Bierut, L.J. and Brown, S.A. and Bucholz, K.K. and Costello, E.J. and de Wit, H. and Diazgranados, N. and Eriksson, J.G. and Farrer, L.A. and Foroud, T.M. and Gillespie, N.A. and Goate, A.M. and Goldman, D. and Grucza, R.A. and Hancock, D.B. and Harris, K.M. and Hesselbrock, V. and Hewitt, J.K. and Hopfer, C.J. and Iacono, W.G. and Johnson, E.O. and Karpyak, V.M. and Kendler, K.S. and Kranzler, H.R. and Krauter, K. and Lind, P.A. and McGue, M. and MacKillop, J. and Madden, P.A.F. and Maes, H.H. and Magnusson, P.K.E. and Nelson, E.C. and Nöthen, M.M. and Palmer, A.A. and Penninx, B.W.J.H. and Porjesz, B. and Rice, J.P. and Rietschel, M. and Riley, B.P. and Rose, R.J. and Shen, P.-H. and Silberg, J. and Stallings, M.C. and Tarter, R.E. and Vanyukov, M.M. and Vrieze, S. and Wall, T.L. and Whitfield, J.B. and Zhao, H. and Neale, B.M. and Wade, T.D. and Heath, A.C. and Montgomery, G.W. and Martin, N.G. and Sullivan, P.F. and Kaprio, J. and Breen, G. and Gelernter, J. and Edenberg, H.J. and Bulik, C.M. and Agrawal, A.",
    journal = "Addiction Biology",
    year = "2021",
    volume = "26",
    number = "1",
    publisher = "Wiley-Blackwell Publishing Ltd",
    issn = "1355-6215, 1369-1600",
    doi = "10.1111/adb.12880",
    keywords = "alcoholism;  anorexia nervosa;  Article;  binge eating disorder;  bulimia;  cannabis addiction;  cannabis use;  controlled study;  drug dependence;  eating disorder;  gene linkage disequilibrium;  gene locus;  genetic association;  genetic correlation;  genetic risk;  genome-wide association study;  human;  major clinical study;  major depression;  phenotype;  priority journal;  regression analysis;  sample size;  schizophrenia;  single nucleotide polymorphism;  smoking;  tobacco dependence;  drug dependence;  eating disorder;  genetics;  phenotype;  risk factor, Alcoholism;  Depressive Disorder, Major;  Feeding and Eating Disorders;  Genome-Wide Association Study;  Humans;  Linkage Disequilibrium;  Phenotype;  Polymorphism, Single Nucleotide;  Risk Factors;  Schizophrenia;  Substance-Related Disorders;  Tobacco Use Disorder",
    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. © 2020 Society for the Study of Addiction"
}