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

Author	: MA Munn-Chernoff EC Johnson YL Chou JRI Coleman LM Thornton RK Walters Z Yilmaz JH Baker C Hübel S Gordon SE Medland HJ Watson HA Gaspar J Bryois A Hinney VM Leppä M Mattheisen S Ripke S Yao P Giusti-Rodríguez KB Hanscombe RAH Adan L Alfredsson T Ando OA Andreassen WH Berrettini I Boehm C Boni Boraska Perica V K Buehren R Burghardt M Cassina S Cichon M Clementi RD Cone P Courtet S Crow JJ Crowley UN Danner OSP Davis M de Zwaan G Dedoussis D Degortes JE DeSocio DM Dick D Dikeos C Dina M Dmitrzak-Węglarz E Docampo LE Duncan K Egberts S Ehrlich G Escaramís T Esko X Estivill A Farmer A Favaro F Fernandez-Aranda MM Fichter K Fischer M Föcker L Foretova AJ Forstner M Forzan CS Franklin S Gallinger I Giegling J Giuranna F Gonidakis P Gorwood Gratacos Mayora S Guillaume Y Guo H Hakonarson K Hatzikotoulas J Hauser J Hebebrand SG Helder S Herms B Herpertz-Dahlmann W Herzog LM Huckins JI Hudson H Imgart H Inoko Janout V S Jimenez-Murcia A Julià G Kalsi D Kaminská L Karhunen A Karwautz MJH Kas JL Kennedy A Keski-Rahkonen K Kiezebrink YR Kim KL Klump GPS Knudsen MC La Via S Le Hellard RD Levitan D Li L Lilenfeld BD Lin J Lissowska J Luykx PJ Magistretti M Maj K Mannik S Marsal CR Marshall M Mattingsdal S McDevitt P McGuffin A Metspalu I Meulenbelt N Micali K Mitchell AM Monteleone P Monteleone B Nacmias M Navratilova I Ntalla JK O'Toole RA Ophoff L Padyukov A Palotie J Pantel H Papezova D Pinto R Rabionet A Raevuori N Ramoz T Reichborn-Kjennerud Ricca V S Ripatti F Ritschel M Roberts A Rotondo D Rujescu F Rybakowski P Santonastaso A Scherag SW Scherer U Schmidt NJ Schork A Schosser J Seitz L Slachtova PE Slagboom MCT Landt A Slopien S Sorbi B Świątkowska JP Szatkiewicz I Tachmazidou E Tenconi A Tortorella F Tozzi J Treasure A Tsitsika M Tyszkiewicz-Nwafor K Tziouvas AA van Elburg EF van Furth G Wagner E Walton E Widen E Zeggini S Zerwas S Zipfel AW Bergen JM Boden H Brandt S Crawford KA Halmi LJ Horwood C Johnson AS Kaplan WH Kaye J Mitchell CM Olsen JF Pearson NL Pedersen M Strober T Werge DC Whiteman DB Woodside J Grove AK Henders JT Larsen R Parker LV Petersen J Jordan MA Kennedy A Birgegård P Lichtenstein C Norring M Landén PB Mortensen R Polimanti JN McClintick AE Adkins F Aliev SA Bacanu A Batzler S Bertelsen JM Biernacka TB Bigdeli LS Chen TK Clarke F Degenhardt AR Docherty AC Edwards JC Foo L Fox J Frank LM Hack AM Hartmann SM Hartz S Heilmann-Heimbach C Hodgkinson P Hoffmann JJ Hottenga B Konte J Lahti M Lahti-Pulkkinen D Lai L Ligthart A Loukola BS Maher H Mbarek AM McIntosh MB McQueen JL Meyers Y Milaneschi T Palviainen RE Peterson E Ryu NL Saccone JE Salvatore S Sanchez-Roige M Schwandt R Sherva F Streit J Strohmaier N Thomas JC Wang BT Webb R Wedow L Wetherill AG Wills H Zhou JD Boardman D Chen DS Choi WE Copeland RC Culverhouse N Dahmen L Degenhardt BW Domingue MA Frye W Gaebel C Hayward M Ising M Keyes F Kiefer G Koller J Kramer S Kuperman S Lucae MT Lynskey W Maier K Mann S Mannisto B Müller-Myhsok AD Murray JI Nurnberger U Preuss K Räikkönen MD Reynolds M Ridinger N Scherbaum MA Schuckit M Soyka J Treutlein SH Witt N Wodarz P Zill DE Adkins DI Boomsma LJ Bierut SA Brown KK Bucholz EJ Costello H de Wit N Diazgranados JG Eriksson LA Farrer TM Foroud NA Gillespie AM Goate D Goldman RA Grucza DB Hancock KM Harris Hesselbrock V JK Hewitt CJ Hopfer WG Iacono EO Johnson VM Karpyak KS Kendler HR Kranzler K Krauter PA Lind M McGue J Mackillop PAF Madden HH Maes PKE Magnusson EC Nelson MM Nöthen AA Palmer BWJH Penninx B Porjesz JP Rice M Rietschel BP Riley RJ Rose PH Shen J Silberg MC Stallings RE Tarter MM Vanyukov S Vrieze TL Wall JB Whitfield H Zhao BM Neale TD Wade AC Heath GW Montgomery NG Martin PF Sullivan J Kaprio G Breen J Gelernter HJ Edenberg CM Bulik A Agrawal
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 ], 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 = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r = 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 = -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.
Year of Publication	: 2020
Journal	: Addiction biology
Number of Pages	: e12880
Date Published	: 2020
ISSN Number	: 1355-6215
URL	: https://doi.org/10.1111/adb.12880
DOI	: 10.1111/adb.12880
Short Title	: Addict Biol
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