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.
Original language | English |
---|---|
Article number | e12880 |
Journal | Addiction Biology |
Volume | 26 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2021 |
Keywords
- eating disorders
- genetic correlation
- substance use
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In: Addiction Biology, Vol. 26, No. 1, e12880, 01.2021.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Shared genetic risk between eating disorder- and substance-use-related phenotypes
T2 - Evidence from genome-wide association studies
AU - Munn-Chernoff, Melissa A.
AU - Johnson, Emma C.
AU - Chou, Yi Ling
AU - Coleman, Jonathan R.I.
AU - Thornton, Laura M.
AU - Walters, Raymond K.
AU - Yilmaz, Zeynep
AU - Baker, Jessica H.
AU - Hübel, Christopher
AU - Gordon, Scott
AU - Medland, Sarah E.
AU - Watson, Hunna J.
AU - Gaspar, Héléna A.
AU - Bryois, Julien
AU - Hinney, Anke
AU - Leppä, Virpi M.
AU - Mattheisen, Manuel
AU - Ripke, Stephan
AU - Yao, Shuyang
AU - Giusti-Rodríguez, Paola
AU - Hanscombe, Ken B.
AU - Adan, Roger A.H.
AU - Alfredsson, Lars
AU - Ando, Tetsuya
AU - Andreassen, Ole A.
AU - Berrettini, Wade H.
AU - Boehm, Ilka
AU - Boni, Claudette
AU - Boraska Perica, Vesna
AU - Buehren, Katharina
AU - Burghardt, Roland
AU - Cassina, Matteo
AU - Cichon, Sven
AU - Clementi, Maurizio
AU - Cone, Roger D.
AU - Courtet, Philippe
AU - Crow, Scott
AU - Crowley, James J.
AU - Danner, Unna N.
AU - Davis, Oliver S.P.
AU - de Zwaan, Martina
AU - Dedoussis, George
AU - Degortes, Daniela
AU - DeSocio, Janiece E.
AU - Dick, Danielle M.
AU - Dikeos, Dimitris
AU - Dina, Christian
AU - Dmitrzak-Weglarz, Monika
AU - Docampo, Elisa
AU - Duncan, Laramie E.
AU - Egberts, Karin
AU - Ehrlich, Stefan
AU - Escaramís, Geòrgia
AU - Esko, Tõnu
AU - Estivill, Xavier
AU - Farmer, Anne
AU - Favaro, Angela
AU - Fernández-Aranda, Fernando
AU - Fichter, Manfred M.
AU - Fischer, Krista
AU - Föcker, Manuel
AU - Foretova, Lenka
AU - Forstner, Andreas J.
AU - Forzan, Monica
AU - Franklin, Christopher S.
AU - Gallinger, Steven
AU - Giegling, Ina
AU - Giuranna, Johanna
AU - Gonidakis, Fragiskos
AU - Gorwood, Philip
AU - Gratacos Mayora, Monica
AU - Guillaume, Sébastien
AU - Guo, Yiran
AU - Hakonarson, Hakon
AU - Hatzikotoulas, Konstantinos
AU - Hauser, Joanna
AU - Hebebrand, Johannes
AU - Helder, Sietske G.
AU - Herms, Stefan
AU - Herpertz-Dahlmann, Beate
AU - Herzog, Wolfgang
AU - Huckins, Laura M.
AU - Hudson, James I.
AU - Imgart, Hartmut
AU - Inoko, Hidetoshi
AU - Janout, Vladimir
AU - Jiménez-Murcia, Susana
AU - Julià, Antonio
AU - Kalsi, Gursharan
AU - Kaminská, Deborah
AU - Karhunen, Leila
AU - Karwautz, Andreas
AU - Kas, Martien J.H.
AU - Kennedy, James L.
AU - Keski-Rahkonen, Anna
AU - Kiezebrink, Kirsty
AU - Kim, Youl Ri
AU - Klump, Kelly L.
AU - Knudsen, Gun Peggy S.
AU - La Via, Maria C.
AU - Le Hellard, Stephanie
AU - Levitan, Robert D.
AU - Li, Dong
AU - Lilenfeld, Lisa
AU - Lin, Bochao Danae
AU - Lissowska, Jolanta
AU - Luykx, Jurjen
AU - Magistretti, Pierre J.
AU - Maj, Mario
AU - Mannik, Katrin
AU - Marsal, Sara
AU - Marshall, Christian R.
AU - Mattingsdal, Morten
AU - McDevitt, Sara
AU - McGuffin, Peter
AU - Metspalu, Andres
AU - Meulenbelt, Ingrid
AU - Micali, Nadia
AU - Mitchell, Karen
AU - Monteleone, Alessio Maria
AU - Monteleone, Palmiero
AU - Nacmias, Benedetta
AU - Navratilova, Marie
AU - Ntalla, Ioanna
AU - O'Toole, Julie K.
AU - Ophoff, Roel A.
AU - Padyukov, Leonid
AU - Palotie, Aarno
AU - Pantel, Jacques
AU - Papezova, Hana
AU - Pinto, Dalila
AU - Rabionet, Raquel
AU - Raevuori, Anu
AU - Ramoz, Nicolas
AU - Reichborn-Kjennerud, Ted
AU - Ricca, Valdo
AU - Ripatti, Samuli
AU - Ritschel, Franziska
AU - Roberts, Marion
AU - Rotondo, Alessandro
AU - Rujescu, Dan
AU - Rybakowski, Filip
AU - Santonastaso, Paolo
AU - Scherag, André
AU - Scherer, Stephen W.
AU - Schmidt, Ulrike
AU - Schork, Nicholas J.
AU - Schosser, Alexandra
AU - Seitz, Jochen
AU - Slachtova, Lenka
AU - Slagboom, P. Eline
AU - Slof-Op't Landt, Margarita C.T.
AU - Slopien, Agnieszka
AU - Sorbi, Sandro
AU - Świątkowska, Beata
AU - Szatkiewicz, Jin P.
AU - Tachmazidou, Ioanna
AU - Tenconi, Elena
AU - Tortorella, Alfonso
AU - Tozzi, Federica
AU - Treasure, Janet
AU - Tsitsika, Artemis
AU - Tyszkiewicz-Nwafor, Marta
AU - Tziouvas, Konstantinos
AU - van Elburg, Annemarie A.
AU - van Furth, Eric F.
AU - Wagner, Gudrun
AU - Walton, Esther
AU - Widen, Elisabeth
AU - Zeggini, Eleftheria
AU - Zerwas, Stephanie
AU - Zipfel, Stephan
AU - Bergen, Andrew W.
AU - Boden, Joseph M.
AU - Brandt, Harry
AU - Crawford, Steven
AU - Halmi, Katherine A.
AU - Horwood, L. John
AU - Johnson, Craig
AU - Kaplan, Allan S.
AU - Kaye, Walter H.
AU - Mitchell, James
AU - Olsen, Catherine M.
AU - Pearson, John F.
AU - Pedersen, Nancy L.
AU - Strober, Michael
AU - Werge, Thomas
AU - Whiteman, David C.
AU - Woodside, D. Blake
AU - Grove, Jakob
AU - Henders, Anjali K.
AU - Larsen, Janne T.
AU - Parker, Richard
AU - Petersen, Liselotte V.
AU - Jordan, Jennifer
AU - Kennedy, Martin A.
AU - Birgegård, Andreas
AU - Lichtenstein, Paul
AU - Norring, Claes
AU - Landén, Mikael
AU - Mortensen, Preben Bo
AU - Polimanti, Renato
AU - McClintick, Jeanette N.
AU - Adkins, Amy E.
AU - Aliev, Fazil
AU - Bacanu, Silviu Alin
AU - Batzler, Anthony
AU - Bertelsen, Sarah
AU - Biernacka, Joanna M.
AU - Bigdeli, Tim B.
AU - Chen, Li Shiun
AU - Clarke, Toni Kim
AU - Degenhardt, Franziska
AU - Docherty, Anna R.
AU - Edwards, Alexis C.
AU - Foo, Jerome C.
AU - Fox, Louis
AU - Frank, Josef
AU - Hack, Laura M.
AU - Hartmann, Annette M.
AU - Hartz, Sarah M.
AU - Heilmann-Heimbach, Stefanie
AU - Hodgkinson, Colin
AU - Hoffmann, Per
AU - Hottenga, Jouke Jan
AU - Konte, Bettina
AU - Lahti, Jari
AU - Lahti-Pulkkinen, Marius
AU - Lai, Dongbing
AU - Ligthart, Lannie
AU - Loukola, Anu
AU - Maher, Brion S.
AU - Mbarek, Hamdi
AU - McIntosh, Andrew M.
AU - McQueen, Matthew B.
AU - Meyers, Jacquelyn L.
AU - Milaneschi, Yuri
AU - Palviainen, Teemu
AU - Peterson, Roseann E.
AU - Ryu, Euijung
AU - Saccone, Nancy L.
AU - Salvatore, Jessica E.
AU - Sanchez-Roige, Sandra
AU - Schwandt, Melanie
AU - Sherva, Richard
AU - Streit, Fabian
AU - Strohmaier, Jana
AU - Thomas, Nathaniel
AU - Wang, Jen Chyong
AU - Webb, Bradley T.
AU - Wedow, Robbee
AU - Wetherill, Leah
AU - Wills, Amanda G.
AU - Zhou, Hang
AU - Boardman, Jason D.
AU - Chen, Danfeng
AU - Choi, Doo Sup
AU - Copeland, William E.
AU - Culverhouse, Robert C.
AU - Dahmen, Norbert
AU - Degenhardt, Louisa
AU - Domingue, Benjamin W.
AU - Frye, Mark A.
AU - Gäebel, Wolfgang
AU - Hayward, Caroline
AU - Ising, Marcus
AU - Keyes, Margaret
AU - Kiefer, Falk
AU - Koller, Gabriele
AU - Kramer, John
AU - Kuperman, Samuel
AU - Lucae, Susanne
AU - Lynskey, Michael T.
AU - Maier, Wolfgang
AU - Mann, Karl
AU - Männistö, Satu
AU - Müller-Myhsok, Bertram
AU - Murray, Alison D.
AU - Nurnberger, John I.
AU - Preuss, Ulrich
AU - Räikkönen, Katri
AU - Reynolds, Maureen D.
AU - Ridinger, Monika
AU - Scherbaum, Norbert
AU - Schuckit, Marc A.
AU - Soyka, Michael
AU - Treutlein, Jens
AU - Witt, Stephanie H.
AU - Wodarz, Norbert
AU - Zill, Peter
AU - Adkins, Daniel E.
AU - Boomsma, Dorret I.
AU - Bierut, Laura J.
AU - Brown, Sandra A.
AU - Bucholz, Kathleen K.
AU - Costello, E. Jane
AU - de Wit, Harriet
AU - Diazgranados, Nancy
AU - Eriksson, Johan G.
AU - Farrer, Lindsay A.
AU - Foroud, Tatiana M.
AU - Gillespie, Nathan A.
AU - Goate, Alison M.
AU - Goldman, David
AU - Grucza, Richard A.
AU - Hancock, Dana B.
AU - Harris, Kathleen Mullan
AU - Hesselbrock, Victor
AU - Hewitt, John K.
AU - Hopfer, Christian J.
AU - Iacono, William G.
AU - Johnson, Eric O.
AU - Karpyak, Victor M.
AU - Kendler, Kenneth S.
AU - Kranzler, Henry R.
AU - Krauter, Kenneth
AU - Lind, Penelope A.
AU - McGue, Matt
AU - MacKillop, James
AU - Madden, Pamela A.F.
AU - Maes, Hermine H.
AU - Magnusson, Patrik K.E.
AU - Nelson, Elliot C.
AU - Nöthen, Markus M.
AU - Palmer, Abraham A.
AU - Penninx, Brenda W.J.H.
AU - Porjesz, Bernice
AU - Rice, John P.
AU - Rietschel, Marcella
AU - Riley, Brien P.
AU - Rose, Richard J.
AU - Shen, Pei Hong
AU - Silberg, Judy
AU - Stallings, Michael C.
AU - Tarter, Ralph E.
AU - Vanyukov, Michael M.
AU - Vrieze, Scott
AU - Wall, Tamara L.
AU - Whitfield, John B.
AU - Zhao, Hongyu
AU - Neale, Benjamin M.
AU - Wade, Tracey D.
AU - Heath, Andrew C.
AU - Montgomery, Grant W.
AU - Martin, Nicholas G.
AU - Sullivan, Patrick F.
AU - Kaprio, Jaakko
AU - Breen, Gerome
AU - Gelernter, Joel
AU - Edenberg, Howard J.
AU - Bulik, Cynthia M.
AU - Agrawal, Arpana
N1 - Funding Information: The PGC‐SUD receives support from the National Institute on Drug Abuse and the National Institute of Mental Health via MH109532. We gratefully acknowledge prior support from the National Institute on Alcohol Abuse and Alcoholism. Statistical analyses for the PGC were carried out on the Genetic Cluster Computer ( http://www.geneticcluster.org ) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480‐05‐003) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. Cohort specific acknowledgements may be found in Walters et al (2018) Nature Neuroscience. Funding Information: We thank all study volunteers, study coordinators, and research staff who enabled this study. ANGI: The Anorexia Nervosa Genetics Initiative was an initiative of the Klarman Family Foundation. Additional support was offered by the National Institute of Mental Health. We acknowledge support from the North Carolina Translational and Clinical Sciences Institute (NC TraCS) and the Carolina Data Warehouse. PGC: We are deeply indebted to the investigators who comprise the PGC and to the hundreds of thousands of individuals who have shared their life experiences with PGC investigators and the contributing studies. We are grateful to the Children's Hospital of Philadelphia (CHOP), the Price Foundation Collaborative Group (PFCG), Genetic Consortium for Anorexia Nervosa (GCAN), Wellcome Trust Case‐Control Consortium‐3 (WTCCC‐3), the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), the QSkin Sun and Health Study, Riksät (Swedish National Quality Register for Eating Disorders), the Stockholm Center for Eating Disorders (SCÄ), LifeGene, the UK Biobank, and all PGC‐ED members for their support in providing individual samples used in this study. We thank SURFsara ( http://www.surf.nl ) for support in using the Lisa Compute Cluster. We thank Max Lam, Institute of Mental Health, Singapore, for Ricopili consultation. This study also represents independent research partly funded by the English National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the English Department of Health and Social Care. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). Research reported in this publication was supported by the National Institute of Mental Health of the US National Institutes of Health under Award Number U01MH109514. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health. Funding Information: Grant support for individual authors can be found in Table S10. This study included summary statistics of a genetic study on cannabis use (Pasman et al [2018] Nature Neuroscience). We would like to acknowledge all participating groups of the International Cannabis Consortium, and in particular, the members of the working group including Joelle Pasman, Karin Verweij, Nathan Gillespie, Eske Derks, and Jacqueline Vink. Pasman et al (2018) included data from the UK Biobank resource under application numbers 9905, 16406, and 25331. We thank all study volunteers, study coordinators, and research staff who enabled this study. ANGI: The Anorexia Nervosa Genetics Initiative was an initiative of the Klarman Family Foundation. Additional support was offered by the National Institute of Mental Health. We acknowledge support from the North Carolina Translational and Clinical Sciences Institute (NC TraCS) and the Carolina Data Warehouse. PGC: We are deeply indebted to the investigators who comprise the PGC and to the hundreds of thousands of individuals who have shared their life experiences with PGC investigators and the contributing studies. We are grateful to the Children's Hospital of Philadelphia (CHOP), the Price Foundation Collaborative Group (PFCG), Genetic Consortium for Anorexia Nervosa (GCAN), Wellcome Trust Case-Control Consortium-3 (WTCCC-3), the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), the QSkin Sun and Health Study, Riks?t (Swedish National Quality Register for Eating Disorders), the Stockholm Center for Eating Disorders (SC?), LifeGene, the UK Biobank, and all PGC-ED members for their support in providing individual samples used in this study. We thank SURFsara (http://www.surf.nl) for support in using the Lisa Compute Cluster. We thank Max Lam, Institute of Mental Health, Singapore, for Ricopili consultation. This study also represents independent research partly funded by the English National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the English Department of Health and Social Care. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). Research reported in this publication was supported by the National Institute of Mental Health of the US National Institutes of Health under Award Number U01MH109514. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health. The PGC-SUD receives support from the National Institute on Drug Abuse and the National Institute of Mental Health via MH109532. We gratefully acknowledge prior support from the National Institute on Alcohol Abuse and Alcoholism. Statistical analyses for the PGC were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480-05-003) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. Cohort specific acknowledgements may be found in Walters et al (2018) Nature Neuroscience. Publisher Copyright: © 2020 Society for the Study of Addiction
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - eating disorders
KW - genetic correlation
KW - substance use
UR - http://www.scopus.com/inward/record.url?scp=85079714981&partnerID=8YFLogxK
U2 - 10.1111/adb.12880
DO - 10.1111/adb.12880
M3 - Article
C2 - 32064741
AN - SCOPUS:85079714981
SN - 1355-6215
VL - 26
JO - Addiction Biology
JF - Addiction Biology
IS - 1
M1 - e12880
ER -