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

Journal article
Authors M. A. Munn-Chernoff
E. C. Johnson
Y. L. Chou
J. R. I. Coleman
L. M. Thornton
R. K. Walters
Z. Yilmaz
J. H. Baker
C. Hubel
S. Gordon
S. E. Medland
H. J. Watson
H. A. Gaspar
J. Bryois
A. Hinney
V. M. Leppa
M. Mattheisen
S. Ripke
S. Y. Yao
P. Giusti-Rodriguez
K. B. Hanscombe
Roger A. H. Adan
L. Alfredsson
T. Ando
O. A. Andreassen
W. H. Berrettini
I. Boehm
C. Boni
V. B. Perica
K. Buehren
R. Burghardt
M. Cassina
S. Cichon
M. Clementi
R. D. Cone
P. Courtet
S. Crow
J. J. Crowley
U. N. Danner
O. S. P. Davis
M. de Zwaan
G. Dedoussis
D. Degortes
J. E. DeSocio
D. M. Dick
D. Dikeos
C. Dina
M. Dmitrzak-Weglarz
E. Docampo
L. E. Duncan
K. Egberts
S. Ehrlich
G. Escaramis
T. Esko
X. Estivill
A. Farmer
A. Favaro
F. Fernandez-Aranda
M. M. Fichter
K. Fischer
M. Focker
L. Foretova
A. J. Forstner
M. Forzan
C. S. Franklin
S. Gallinger
I. Giegling
J. Giuranna
F. Gonidakis
P. Gorwood
M. G. Mayora
S. Guillaume
Y. R. Guo
H. Hakonarson
K. Hatzikotoulas
J. Hauser
J. Hebebrand
S. G. Helder
S. Herms
B. Herpertz-Dahlmann
W. Herzog
L. M. Huckins
J. I. Hudson
H. Imgart
H. Inoko
V. Janout
S. Jimenez-Murcia
A. Julia
G. Kalsi
D. Kaminska
L. Karhunen
A. Karwautz
M. J. H. Kas
J. L. Kennedy
A. Keski-Rahkonen
K. Kiezebrink
Y. R. Kim
K. L. Klump
G. P. S. Knudsen
M. C. La Via
S. Le Hellard
R. D. Levitan
D. Li
L. Lilenfeld
B. D. Lin
J. Lissowska
J. Luykx
P. J. Magistretti
M. Maj
K. Mannik
S. Marsal
C. R. Marshall
M. Mattingsdal
S. McDevitt
P. McGuffin
A. Metspalu
I. Meulenbelt
N. Micali
K. Mitchell
A. M. Monteleone
P. Monteleone
B. Nacmias
M. Navratilova
I. Ntalla
J. K. O'Toole
R. A. Ophoff
L. Padyukov
A. Palotie
J. Pantel
H. Papezova
D. Pinto
R. Rabionet
A. Raevuori
N. Ramoz
T. Reichborn-Kjennerud
V. Ricca
S. Ripatti
F. Ritschel
M. Roberts
A. Rotondo
D. Rujescu
F. Rybakowski
P. Santonastaso
A. Scherag
S. W. Scherer
U. Schmidt
N. J. Schork
A. Schosser
J. Seitz
L. Slachtova
P. E. Slagboom
Mctso Landt
A. Slopien
S. Sorbi
B. Swiatkowska
J. P. Szatkiewicz
I. Tachmazidou
E. Tenconi
A. Tortorella
F. Tozzi
J. Treasure
A. Tsitsika
M. Tyszkiewicz-Nwafor
K. Tziouvas
A. A. van Elburg
E. F. van Furth
G. Wagner
E. Walton
E. Widen
E. Zeggini
S. Zerwas
S. Zipfel
A. W. Bergen
J. M. Boden
H. Brandt
S. Crawford
K. A. Halmi
L. J. Horwood
C. Johnson
A. S. Kaplan
W. H. Kaye
J. Mitchell
C. M. Olsen
J. F. Pearson
N. L. Pedersen
M. Strober
T. Werge
D. C. Whiteman
D. B. Woodside
J. Grove
A. K. Henders
J. T. Larsen
R. Parker
L. V. Petersen
J. Jordan
M. A. Kennedy
A. Birgegard
P. Lichtenstein
C. Norring
Mikael Landén
P. B. Mortensen
R. Polimanti
J. N. McClintick
A. E. Adkins
F. Aliev
S. A. Bacanu
A. Batzler
S. Bertelsen
J. M. Biernacka
T. B. Bigdeli
L. S. Chen
T. K. Clarke
F. Degenhardt
A. R. Docherty
A. C. Edwards
J. C. Foo
L. Fox
J. Frank
L. M. Hack
A. M. Hartmann
S. M. Hartz
S. Heilmann-Heimbach
C. Hodgkinson
P. Hoffmann
J. J. Hottenga
B. Konte
J. Lahti
M. Lahti-Pulkkinen
D. B. Lai
L. Ligthart
A. Loukola
B. S. Maher
H. Mbarek
A. M. McIntosh
M. B. McQueen
J. L. Meyers
Y. Milaneschi
T. Palviainen
R. E. Peterson
E. Ryu
N. L. Saccone
J. E. Salvatore
S. Sanchez-Roige
M. Schwandt
R. Sherva
F. Streit
J. Strohmaier
N. Thomas
J. C. Wang
B. T. Webb
R. Wedow
L. Wetherill
A. G. Wills
H. Zhou
J. D. Boardman
D. F. Chen
D. S. Choi
W. E. Copeland
R. C. Culverhouse
N. Dahmen
L. Degenhardt
B. W. Domingue
M. A. Frye
W. Gabel
C. Hayward
M. Ising
M. Keyes
F. Kiefer
G. Koller
J. Kramer
S. Kuperman
S. Lucae
M. T. Lynskey
W. Maier
K. Mann
S. Mannisto
B. Muller-Myhsok
A. D. Murray
J. I. Nurnberger
U. Preuss
K. Raikkonen
M. D. Reynolds
M. Ridinger
N. Scherbaum
M. A. Schuckit
M. Soyka
J. Treutlein
S. H. Witt
N. Wodarz
P. Zill
D. E. Adkins
D. I. Boomsma
L. J. Bierut
S. A. Brown
K. K. Bucholz
E. J. Costello
H. de Wit
N. Diazgranados
J. G. Eriksson
L. A. Farrer
T. M. Foroud
N. A. Gillespie
A. M. Goate
D. Goldman
R. A. Grucza
D. B. Hancock
K. M. Harris
V. Hesselbrock
J. K. Hewitt
C. J. Hopfer
W. G. Iacono
E. O. Johnson
V. M. Karpyak
K. S. Kendler
H. R. Kranzler
K. Krauter
P. A. Lind
M. McGue
J. MacKillop
P. A. F. Madden
H. H. Maes
P. K. E. Magnusson
E. C. Nelson
M. M. Nothen
A. A. Palmer
Bwjh Penninx
B. Porjesz
J. P. Rice
M. Rietschel
B. P. Riley
R. J. Rose
P. H. Shen
J. Silberg
M. C. Stallings
R. E. Tarter
M. M. Vanyukov
S. Vrieze
T. L. Wall
J. B. Whitfield
H. Y. Zhao
B. M. Neale
T. D. Wade
A. C. Heath
G. W. Montgomery
N. G. Martin
P. F. Sullivan
J. Kaprio
G. Breen
J. Gelernter
H. J. Edenberg
C. M. Bulik
A. Agrawal
Published in Addiction Biology
ISSN 1355-6215
Publication year 2020
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Language en
Links dx.doi.org/10.1111/adb.12880
Keywords eating disorders, genetic correlation, substance use, alcohol dependence, anorexia-nervosa, drug-use, environmental, contributions, bulimia-nervosa, women, gwas, twin, endocannabinoids, comorbidity, Biochemistry & Molecular Biology, Substance Abuse
Subject categories Biochemistry and Molecular Biology

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 similar to 2400 to similar 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.

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