Menu Close

Shared Genetic Risk between Eating Disorder- and Substance-Use-Related Phenotypes: Evidence from Genome-Wide Association Studies

Citation

Munn-Chernoff, Melissa A.; Johnson, Emma C.; Chou, Yi-Ling; Coleman, Jonathan R. I.; Thornton, Laura M.; Walters, Raymond K.; Yilmaz, Zeynep; Baker, Jessica H.; Hübel, Christopher; & Gordon, Scott D., et al. (Online ahead of print). Shared Genetic Risk between Eating Disorder- and Substance-Use-Related Phenotypes: Evidence from Genome-Wide Association Studies. Addiction Biology. PMCID: PMC7429266

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.

URL

http://dx.doi.org/10.1111/adb.12880

Reference Type

Journal Article

Journal Title

Addiction Biology

Author(s)

Munn-Chernoff, Melissa A.
Johnson, Emma C.
Chou, Yi-Ling
Coleman, Jonathan R. I.
Thornton, Laura M.
Walters, Raymond K.
Yilmaz, Zeynep
Baker, Jessica H.
Hübel, Christopher
Gordon, Scott D.
Medland, Sarah E.
Watson, Hunna J.
Gaspar, Héléna A.
Bryois, Julien
Hinney, Anke
Leppä, Virpi M.
Mattheisen, Manuel
Ripke, Stephan
Yao, Shuyang
Giusti-Rodríguez, Paola
Hanscombe, Ken B.
Adan, Roger A. H.
Alfredsson, Lars
Ando, Tetsuya
Andreassen, Ole A.
Berrettini, Wade H.
Boehm, Ilka
Boni, Claudette
Boraska Perica, Vesna
Buehren, Katharina
Burghardt, Roland
Cassina, Matteo
Cichon, Sven
Clementi, Maurizio
Cone, Roger D.
Courtet, Philippe
Crow, Scott
Crowley, James J.
Danner, Unna N.
Davis, Oliver S. P.
de Zwaan, Martina H.
Dedoussis, George
Degortes, Daniela
DeSocio, Janiece E.
Dick, Danielle M.
Dikeos, Dimitris
Dina, Christian
Dmitrzak-Weglarz, Monika
Docampo, Elisa
Duncan, Laramie E.
Egberts, Karin M.
Ehrlich, Stefan
Escaramís, Geòrgia
Esko, Tõnu
Estivill, Xavier
Farmer, Anne
Favaro, Angela
Fernández-Aranda, Fernando
Fichter, Manfred M.
Fischer, Krista
Föcker, Manuel
Foretova, Lenka
Forstner, Andreas J.
Forzan, Monica
Franklin, Christopher S.
Gallinger, Steven J.
Giegling, Ina
Giuranna, Johanna
Gonidakis, Fragiskos
Gorwood, Philip
Gratacos Mayora, Monica
Guillaume, Sébastien
Guo, Yiran
Hakonarson, Hakon
Hatzikotoulas, Konstantinos
Hauser, Joanna
Hebebrand, Johannes
Helder, Sietske G.
Herms, Stefan
Herpertz-Dahlmann, Beate
Herzog, Wolfgang
Huckins, Laura M.
Hudson, James I.
Imgart, Hartmut
Inoko, Hidetoshi
Janout, Vladimir
Jiménez-Murcia, Susana
Julià, Antonio
Kalsi, Gursharan
Kaminská, Deborah
Karhunen, Leila
Karwautz, Andreas
Kas, Martien J. H.
Kennedy, James L.
Keski-Rahkonen, Anna
Kiezebrink, Kirsty
Kim, Youl-Ri
Klump, Kelly L.
Knudsen, Gun Peggy S.
La Via, Maria C.
Le Hellard, Stephanie
Levitan, Robert D.
Li, Dong
Lilenfeld, Lisa
Lin, Bochao Danae
Lissowska, Jolanta
Luykx, Jurjen
Magistretti, Pierre J.
Maj, Mario
Mannik, Katrin
Marsal, Sara
Marshall, Christian R.
Mattingsdal, Morten
McDevitt, Sara
McGuffin, Peter
Metspalu, Andres
Meulenbelt, Ingrid
Micali, Nadia
Mitchell, Karen S.
Monteleone, Alessio Maria
Monteleone, Palmiero
Nacmias, Benedetta
Navratilova, Marie
Ntalla, Ioanna
O'Toole, Julie K.
Ophoff, Roel A.
Padyukov, Leonid
Palotie, Aarno
Pantel, Jacques
Papezova, Hana
Pinto, Dalila
Rabionet, Raquel
Raevuori, Anu
Ramoz, Nicolas
Reichborn-Kjennerud, Ted
Ricca, Valdo
Ripatti, Samuli
Ritschel, Franziska
Roberts, Marion
Rotondo, Alessandro
Rujescu, Dan
Rybakowski, Filip
Santonastaso, Paolo
Scherag, André
Scherer, Stephen W.
Schmidt, Ulrike
Schork, Nicholas J.
Schosser, Alexandra
Seitz, Jochen
Slachtova, Lenka
Slagboom, P. Eline
Slof-Op't Landt, Margarita C. T.
Slopien, Agnieszka
Sorbi, Sandro
Świątkowska, Beata
Szatkiewicz, Jin P.
Tachmazidou, Ioanna
Tenconi, Elena
Tortorella, Alfonso
Tozzi, Federica
Treasure, Janet
Tsitsika, Artemis
Tyszkiewicz-Nwafor, Marta
Tziouvas, Konstantinos
van Elburg, Annemarie A.
van Furth, Eric F.
Wagner, Gudrun
Walton, Esther
Widen, Elisabeth
Zeggini, Eleftheria
Zerwas, Stephanie
Zipfel, Stephan
Bergen, Andrew W.
Boden, Joseph M.
Brandt, Harry
Crawford, Steven
Halmi, Katherine A.
Horwood, L. John
Johnson, Craig
Kaplan, Allan S.
Kaye, Walter H.
Mitchell, James
Olsen, Catherine M.
Pearson, John F.
Pedersen, Nancy L.
Strober, Michael
Werge, Thomas
Whiteman, David C.
Woodside, D. Blake
Grove, Jakob
Henders, Anjali K.
Larsen, Janne T.
Parker, Richard
Petersen, Liselotte V.
Jordan, Jennifer
Kennedy, Martin A.
Birgegård, Andreas
Lichtenstein, Paul
Norring, Claes
Landén, Mikael
Mortensen, Preben Bo
Polimanti, Renato
McClintick, Jeanette N.
Adkins, Amy E.
Aliev, Fazil
Bacanu, Silviu-Alin
Batzler, Anthony
Bertelsen, Sarah
Biernacka, Joanna M.
Bigdeli, Tim B.
Chen, Li-Shiun
Clarke, Toni-Kim
Degenhardt, Franziska
Docherty, Anna R.
Edwards, Alexis C.
Foo, Jerome C.
Fox, Louis
Frank, Josef
Hack, Laura M.
Hartmann, Annette M.
Hartz, Sarah M.
Heilmann-Heimbach, Stefanie
Hodgkinson, Colin
Hoffmann, Per
Hottenga, Jouke-Jan
Konte, Bettina
Lahti, Jari
Lahti-Pulkkinen, Marius
Lai, Dongbing
Ligthart, Lannie
Loukola, Anu
Maher, Brion S.
Mbarek, Hamdi
McIntosh, Andrew M.
McQueen, Matthew B.
Meyers, Jacquelyn L.
Milaneschi, Yuri
Palviainen, Teemu
Peterson, Roseann E.
Ryu, Euijung
Saccone, Nancy L.
Salvatore, Jessica E.
Sanchez-Roige, Sandra
Schwandt, Melanie
Sherva, Richard
Streit, Fabian
Strohmaier, Jana
Thomas, Nathaniel
Wang, Jen-Chyong
Webb, Bradley T.
Wedow, Robbee
Wetherill, Leah
Wills, Amanda G.
Zhou, Hang
Boardman, Jason D.
Chen, Danfeng
Choi, Doo-Sup
Copeland, William E.
Culverhouse, Robert C.
Dahmen, Norbert
Degenhardt, Louisa
Domingue, Benjamin W.
Frye, Mark A.
Gäbel, Wolfgang
Hayward, Caroline
Ising, Marcus
Keyes, Margaret
Kiefer, Falk
Koller, Gabriele
Kramer, John
Kuperman, Samuel
Lucae, Susanne
Lynskey, Michael T.
Maier, Wolfgang
Mann, Karl
Männistö, Satu
Müller-Myhsok, Bertram
Murray, Alison D.
Nurnberger, John I.
Preuss, Ulrich
Räikkönen, Katri
Reynolds, Maureen D.
Ridinger, Monika
Scherbaum, Norbert
Schuckit, Marc A.
Soyka, Michael
Treutlein, Jens
Witt, Stephanie H.
Wodarz, Norbert
Zill, Peter
Adkins, Daniel E.
Boomsma, Dorret I.
Bierut, Laura J.
Brown, Sandra A.
Bucholz, Kathleen K.
Costello, E. Jane
de Wit, Harriet
Diazgranados, Nancy
Eriksson, Johan G.
Farrer, Lindsay A.
Foroud, Tatiana M.
Gillespie, Nathan A.
Goate, Alison M.
Goldman, David
Grucza, Richard A.
Hancock, Dana B.
Harris, Kathleen Mullan
Hesselbrock, Victor
Hewitt, John K.
Hopfer, Christian J.
Iacono, William G.
Johnson, Eric O.
Karpyak, Victor M.
Kendler, Kenneth S.
Kranzler, Henry R.
Krauter, Kenneth S.
Lind, Penelope A.
McGue, Matt
MacKillop, James
Madden, Pamela A. F.
Maes, Hermine H.
Magnusson, Patrik K. E.
Nelson, Elliot C.
Nöthen, Markus M.
Palmer, Abraham A.
Penninx, Brenda W. J. H. W.
Porjesz, Bernice
Rice, John P.
Rietschel, Marcella
Riley, Brien P.
Rose, Richard J.
Shen, Pei-Hong
Silberg, Judy L.
Stallings, Michael C.
Tarter, Ralph E.
Vanyukov, Michael M.
Vrieze, Scott
Wall, Tamara L.
Whitfield, John B.
Zhao, Hongyu
Neale, Benjamin M.
Wade, Tracey D.
Heath, Andrew C.
Montgomery, Grant W.
Martin, Nicholas G.
Sullivan, Patrick F.
Kaprio, Jaakko
Breen, Gerome
Gelernter, Joel E.
Edenberg, Howard J.
Bulik, Cynthia M.
Agrawal, Arpana

Year Published

Online ahead of print

PMCID

PMC7429266

NIHMSID

NIHMS1582438

Reference ID

12649