Addict Biol.: co-auth.: group Reymond

2020 Feb 16:e12880. doi: 10.1111/adb.12880. [Epub ahead of print]

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

Munn-Chernoff MA¹, Johnson EC², Chou YL², Coleman JRI^3,⁴, Thornton LM¹, Walters RK^5,⁶, Yilmaz Z^1,⁷, Baker JH¹, Hübel C^3,⁸, Gordon S⁹, Medland SE⁹, Watson HJ^1,^10,¹¹, Gaspar HA^3,⁴, Bryois J⁸, Hinney A¹², Leppä VM⁸, Mattheisen M^13,^14,^15,¹⁶, Ripke S^5,^6,¹⁷, Yao S⁸, Giusti-Rodríguez P⁷, Hanscombe KB¹⁸, Adan RAH^19,^20,²¹, Alfredsson L²², Ando T²³, Andreassen OA²⁴, Berrettini WH²⁵, Boehm I²⁶, Boni C²⁷, Boraska Perica V^28,²⁹, Buehren K³⁰, Burghardt R³¹, Cassina M³², Cichon S^33,^34,³⁵, Clementi M³², Cone RD³⁶, Courtet P³⁷, Crow S³⁸, Crowley JJ^7,¹⁴, Danner UN³⁹, Davis OSP^40,⁴¹, de Zwaan M⁴², Dedoussis G⁴³, Degortes D⁴⁴, DeSocio JE⁴⁵, Dick DM^46,^47,⁴⁸, Dikeos D⁴⁹, Dina C⁵⁰, Dmitrzak-Weglarz M⁵¹, Docampo E^52,^53,⁵⁴, Duncan LE⁵⁵, Egberts K⁵⁶, Ehrlich S²⁶, Escaramís G^52,^53,⁵⁴, Esko T^57,⁵⁸, Estivill X^52,^53,^54,⁵⁹, Farmer A³, Favaro A⁴⁴, Fernández-Aranda F^60,⁶¹, Fichter MM^62,⁶³, Fischer K⁵⁷, Föcker M⁶⁴, Foretova L⁶⁵, Forstner AJ^34,^66,^67,⁶⁸, Forzan M³², Franklin CS²⁸, Gallinger S⁶⁹, Giegling I⁷⁰, Giuranna J¹², Gonidakis F⁷¹, Gorwood P^72,⁷³, Gratacos Mayora M^52,^53,⁵⁴, Guillaume S³⁷, Guo Y⁷⁴, Hakonarson H^74,⁷⁵, Hatzikotoulas K^28,⁷⁶, Hauser J⁷⁷, Hebebrand J¹², Helder SG^3,⁷⁸, Herms S^33,³⁴, Herpertz-Dahlmann B³⁰, Herzog W⁷⁹, Huckins LM^28,⁸⁰, Hudson JI⁸¹, Imgart H⁸², Inoko H⁸³, Janout V⁸⁴, Jiménez-Murcia S^60,⁶¹, Julià A⁸⁵, Kalsi G³, Kaminská D⁸⁶, Karhunen L⁸⁷, Karwautz A⁸⁸, Kas MJH^19,⁸⁹, Kennedy JL^90,^91,⁹², Keski-Rahkonen A⁹³, Kiezebrink K⁹⁴, Kim YR⁹⁵, Klump KL⁹⁶, Knudsen GPS⁹⁷, La Via MC¹, Le Hellard S^98,^99,¹⁰⁰, Levitan RD⁹¹, Li D⁷⁴, Lilenfeld L¹⁰¹, Lin BD¹⁹, Lissowska J¹⁰², Luykx J¹⁹, Magistretti PJ^103,¹⁰⁴, Maj M¹⁰⁵, Mannik K^57,¹⁰⁶, Marsal S⁸⁵, Marshall CR¹⁰⁷, Mattingsdal M¹⁰⁸, McDevitt S^109,¹¹⁰, McGuffin P³, Metspalu A^57,¹¹¹, Meulenbelt I¹¹², Micali N^113,¹¹⁴, Mitchell K^115,¹¹⁶, Monteleone AM¹⁰⁵, Monteleone P¹¹⁷, Nacmias B¹¹⁸, Navratilova M⁶⁵, Ntalla I⁴³, O’Toole JK¹¹⁹, Ophoff RA^120,¹²¹, Padyukov L¹²², Palotie A^58,^123,¹²⁴, Pantel J²⁷, Papezova H⁸⁶, Pinto D⁸⁰, Rabionet R^125,^126,¹²⁷, Raevuori A⁹³, Ramoz N²⁷, Reichborn-Kjennerud T^97,¹²⁸, Ricca V¹²⁹, Ripatti S¹³⁰, Ritschel F^26,¹³¹, Roberts M³, Rotondo A¹³², Rujescu D⁷⁰, Rybakowski F¹³³, Santonastaso P¹³⁴, Scherag A¹³⁵, Scherer SW^136,¹³⁷, Schmidt U¹³⁸, Schork NJ¹³⁹, Schosser A¹⁴⁰, Seitz J³⁰, Slachtova L¹⁴¹, Slagboom PE¹⁴², Slof-Op’t Landt MCT^143,¹⁴⁴, Slopien A¹⁴⁵, Sorbi S^118,¹⁴⁶, Świątkowska B¹⁴⁷, Szatkiewicz JP⁷, Tachmazidou I²⁸, Tenconi E⁴⁴, Tortorella A^148,¹⁴⁹, Tozzi F¹⁵⁰, Treasure J¹³⁸, Tsitsika A¹⁵¹, Tyszkiewicz-Nwafor M¹⁴⁵, Tziouvas K¹⁵², van Elburg AA^20,¹⁵³, van Furth EF^143,¹⁴⁴, Wagner G⁸⁸, Walton E²⁶, Widen E¹²³, Zeggini E^28,⁷⁶, Zerwas S¹, Zipfel S¹⁵⁴, Bergen AW^155,¹⁵⁶, Boden JM¹⁵⁷, Brandt H¹⁵⁸, Crawford S¹⁵⁸, Halmi KA¹⁵⁹, Horwood LJ¹⁵⁷, Johnson C¹⁶⁰, Kaplan AS^90,^91,⁹², Kaye WH¹⁶¹, Mitchell J¹⁶², Olsen CM¹⁶³, Pearson JF¹⁶⁴, Pedersen NL⁸, Strober M^165,¹⁶⁶, Werge T¹⁶⁷, Whiteman DC¹⁶³, Woodside DB^91,^92,^168,¹⁶⁹, Grove J^13,^170,^171,¹⁷², Henders AK¹⁷³, Larsen JT^170,^174,¹⁷⁵, Parker R⁹, Petersen LV^170,^174,¹⁷⁵, Jordan J^176,¹⁷⁷, Kennedy MA¹⁷⁸, Birgegård A^8,^14,¹⁵, Lichtenstein P⁸, Norring C^14,¹⁵, Landén M^8,¹⁷⁹, Mortensen PB^170,^174,¹⁷⁵, Polimanti R^180,¹⁸¹, McClintick JN¹⁸², Adkins AE^46,⁴⁷, Aliev F^46,¹⁸³, Bacanu SA^184,^185,¹⁸⁶, Batzler A¹⁸⁷, Bertelsen S¹⁸⁸, Biernacka JM^189,¹⁹⁰, Bigdeli TB¹⁹¹, Chen LS², Clarke TK¹⁹², Degenhardt F¹⁹³, Docherty AR¹⁹⁴, Edwards AC^185,¹⁸⁶, Foo JC¹⁹⁵, Fox L², Frank J¹⁹⁵, Hack LM⁵⁵, Hartmann AM⁷⁰, Hartz SM², Heilmann-Heimbach S¹⁹³, Hodgkinson C¹⁹⁶, Hoffmann P^67,^197,¹⁹⁸, Hottenga JJ¹⁹⁹, Konte B⁷⁰, Lahti J²⁰⁰, Lahti-Pulkkinen M²⁰¹, Lai D²⁰², Ligthart L¹⁹⁹, Loukola A¹²³, Maher BS²⁰³, Mbarek H¹⁹⁹, McIntosh AM²⁰⁴, McQueen MB²⁰⁵, Meyers JL²⁰⁶, Milaneschi Y²⁰⁷, Palviainen T¹²³, Peterson RE^185,¹⁸⁶, Ryu E¹⁹⁰, Saccone NL²⁰⁸, Salvatore JE^46,^185,¹⁸⁶, Sanchez-Roige S¹⁶¹, Schwandt M²⁰⁹, Sherva R²¹⁰, Streit F¹⁹⁵, Strohmaier J¹⁹⁵, Thomas N^46,⁴⁷, Wang JC¹⁸⁸, Webb BT^184,^185,¹⁸⁶, Wedow R^5,^6,^208,²¹¹, Wetherill L²⁰², Wills AG²¹², Zhou H^180,¹⁸¹, Boardman JD^213,²¹⁴, Chen D⁶, Choi DS²¹⁵, Copeland WE²¹⁶, Culverhouse RC²¹⁷, Dahmen N²¹⁸, Degenhardt L²¹⁹, Domingue BW²²⁰, Frye MA¹⁹⁰, Gäbel W²²¹, Hayward C²²², Ising M²²³, Keyes M²²⁴, Kiefer F²²⁵, Koller G²²⁶, Kramer J²²⁷, Kuperman S²²⁸, Lucae S²²³, Lynskey MT²²⁸, Maier W²²⁹, Mann K²²⁵, Männistö S²³⁰, Müller-Myhsok B²³¹, Murray AD²³², Nurnberger JI^203,²³³, Preuss U^234,²³⁵, Räikkönen K²⁰¹, Reynolds MD²³⁶, Ridinger M²³⁷, Scherbaum N²³⁸, Schuckit MA¹⁶¹, Soyka M^239,²⁴⁰, Treutlein J¹⁹⁵, Witt SH¹⁹⁵, Wodarz N²⁴¹, Zill P²⁴², Adkins DE^194,²⁴³, Boomsma DI¹⁹⁹, Bierut LJ², Brown SA^161,²⁴⁴, Bucholz KK², Costello EJ²⁴⁵, de Wit H²⁴⁶, Diazgranados N²⁴⁷, Eriksson JG^248,²⁴⁹, Farrer LA^208,^250,^251,^252,²⁵³, Foroud TM²⁰², Gillespie NA^185,¹⁸⁶, Goate AM¹⁸⁸, Goldman D^196,²⁵⁴, Grucza RA², Hancock DB²⁵⁵, Harris KM^256,²⁵⁷, Hesselbrock V²⁵⁸, Hewitt JK²⁵⁹, Hopfer CJ²⁶⁰, Iacono WG²²⁵, Johnson EO^256,²⁶¹, Karpyak VM¹⁸⁹, Kendler KS^185,¹⁸⁶, Kranzler HR^262,²⁶³, Krauter K²⁶⁴, Lind PA⁹, McGue M²²⁵, MacKillop J^265,²⁶⁶, Madden PAF², Maes HH¹⁸⁵, Magnusson PKE⁸, Nelson EC², Nöthen MM¹⁹³, Palmer AA^161,²⁶⁷, Penninx BWJH²⁶⁸, Porjesz B²⁰⁶, Rice JP², Rietschel M¹⁹⁵, Riley BP^184,^185,¹⁸⁶, Rose RJ²⁶⁹, Shen PH¹⁹⁶, Silberg J^185,¹⁸⁶, Stallings MC²⁶⁰, Tarter RE²³⁷, Vanyukov MM²³⁷, Vrieze S²²⁵, Wall TL¹⁶¹, Whitfield JB⁹, Zhao H²⁷⁰, Neale BM^5,⁶, Wade TD²⁷¹, Heath AC², Montgomery GW^9,^173,²⁷², Martin NG⁹, Sullivan PF^1,^7,⁸, Kaprio J^93,¹²³, Breen G^3,⁴, Gelernter J^180,^181,^273,²⁷⁴, Edenberg HJ^182,²⁰², Bulik CM^1,^8,²⁷⁴, Agrawal A².

Author information

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.

KEYWORDS:

eating disorders; genetic correlation; substance use

PMID: 32064741