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 MA1Johnson EC2Chou YL2Coleman JRI3,4Thornton LM1Walters RK5,6Yilmaz Z1,7Baker JH1Hübel C3,8Gordon S9Medland SE9Watson HJ1,10,11Gaspar HA3,4Bryois J8Hinney A12Leppä VM8Mattheisen M13,14,15,16Ripke S5,6,17Yao S8Giusti-Rodríguez P7Hanscombe KB18Adan RAH19,20,21Alfredsson L22Ando T23Andreassen OA24Berrettini WH25Boehm I26Boni C27Boraska Perica V28,29Buehren K30Burghardt R31Cassina M32Cichon S33,34,35Clementi M32Cone RD36Courtet P37Crow S38Crowley JJ7,14Danner UN39Davis OSP40,41de Zwaan M42Dedoussis G43Degortes D44DeSocio JE45Dick DM46,47,48Dikeos D49Dina C50Dmitrzak-Weglarz M51Docampo E52,53,54Duncan LE55Egberts K56Ehrlich S26Escaramís G52,53,54Esko T57,58Estivill X52,53,54,59Farmer A3Favaro A44Fernández-Aranda F60,61Fichter MM62,63Fischer K57Föcker M64Foretova L65Forstner AJ34,66,67,68Forzan M32Franklin CS28Gallinger S69Giegling I70Giuranna J12Gonidakis F71Gorwood P72,73Gratacos Mayora M52,53,54Guillaume S37Guo Y74Hakonarson H74,75Hatzikotoulas K28,76Hauser J77Hebebrand J12Helder SG3,78Herms S33,34Herpertz-Dahlmann B30Herzog W79Huckins LM28,80Hudson JI81Imgart H82Inoko H83Janout V84Jiménez-Murcia S60,61Julià A85Kalsi G3Kaminská D86Karhunen L87Karwautz A88Kas MJH19,89Kennedy JL90,91,92Keski-Rahkonen A93Kiezebrink K94Kim YR95Klump KL96Knudsen GPS97La Via MC1Le Hellard S98,99,100Levitan RD91Li D74Lilenfeld L101Lin BD19Lissowska J102Luykx J19Magistretti PJ103,104Maj M105Mannik K57,106Marsal S85Marshall CR107Mattingsdal M108McDevitt S109,110McGuffin P3Metspalu A57,111Meulenbelt I112Micali N113,114Mitchell K115,116Monteleone AM105Monteleone P117Nacmias B118Navratilova M65Ntalla I43O’Toole JK119Ophoff RA120,121Padyukov L122Palotie A58,123,124Pantel J27Papezova H86Pinto D80Rabionet R125,126,127Raevuori A93Ramoz N27Reichborn-Kjennerud T97,128Ricca V129Ripatti S130Ritschel F26,131Roberts M3Rotondo A132Rujescu D70Rybakowski F133Santonastaso P134Scherag A135Scherer SW136,137Schmidt U138Schork NJ139Schosser A140Seitz J30Slachtova L141Slagboom PE142Slof-Op’t Landt MCT143,144Slopien A145Sorbi S118,146Świątkowska B147Szatkiewicz JP7Tachmazidou I28Tenconi E44Tortorella A148,149Tozzi F150Treasure J138Tsitsika A151Tyszkiewicz-Nwafor M145Tziouvas K152van Elburg AA20,153van Furth EF143,144Wagner G88Walton E26Widen E123Zeggini E28,76Zerwas S1Zipfel S154Bergen AW155,156Boden JM157Brandt H158Crawford S158Halmi KA159Horwood LJ157Johnson C160Kaplan AS90,91,92Kaye WH161Mitchell J162Olsen CM163Pearson JF164Pedersen NL8Strober M165,166Werge T167Whiteman DC163Woodside DB91,92,168,169Grove J13,170,171,172Henders AK173Larsen JT170,174,175Parker R9Petersen LV170,174,175Jordan J176,177Kennedy MA178Birgegård A8,14,15Lichtenstein P8Norring C14,15Landén M8,179Mortensen PB170,174,175Polimanti R180,181McClintick JN182Adkins AE46,47Aliev F46,183Bacanu SA184,185,186Batzler A187Bertelsen S188Biernacka JM189,190Bigdeli TB191Chen LS2Clarke TK192Degenhardt F193Docherty AR194Edwards AC185,186Foo JC195Fox L2Frank J195Hack LM55Hartmann AM70Hartz SM2Heilmann-Heimbach S193Hodgkinson C196Hoffmann P67,197,198Hottenga JJ199Konte B70Lahti J200Lahti-Pulkkinen M201Lai D202Ligthart L199Loukola A123Maher BS203Mbarek H199McIntosh AM204McQueen MB205Meyers JL206Milaneschi Y207Palviainen T123Peterson RE185,186Ryu E190Saccone NL208Salvatore JE46,185,186Sanchez-Roige S161Schwandt M209Sherva R210Streit F195Strohmaier J195Thomas N46,47Wang JC188Webb BT184,185,186Wedow R5,6,208,211Wetherill L202Wills AG212Zhou H180,181Boardman JD213,214Chen D6Choi DS215Copeland WE216Culverhouse RC217Dahmen N218Degenhardt L219Domingue BW220Frye MA190Gäbel W221Hayward C222Ising M223Keyes M224Kiefer F225Koller G226Kramer J227Kuperman S228Lucae S223Lynskey MT228Maier W229Mann K225Männistö S230Müller-Myhsok B231Murray AD232Nurnberger JI203,233Preuss U234,235Räikkönen K201Reynolds MD236Ridinger M237Scherbaum N238Schuckit MA161Soyka M239,240Treutlein J195Witt SH195Wodarz N241Zill P242Adkins DE194,243Boomsma DI199Bierut LJ2Brown SA161,244Bucholz KK2Costello EJ245de Wit H246Diazgranados N247Eriksson JG248,249Farrer LA208,250,251,252,253Foroud TM202Gillespie NA185,186Goate AM188Goldman D196,254Grucza RA2Hancock DB255Harris KM256,257Hesselbrock V258Hewitt JK259Hopfer CJ260Iacono WG225Johnson EO256,261Karpyak VM189Kendler KS185,186Kranzler HR262,263Krauter K264Lind PA9McGue M225MacKillop J265,266Madden PAF2Maes HH185Magnusson PKE8Nelson EC2Nöthen MM193Palmer AA161,267Penninx BWJH268Porjesz B206Rice JP2Rietschel M195Riley BP184,185,186Rose RJ269Shen PH196Silberg J185,186Stallings MC260Tarter RE237Vanyukov MM237Vrieze S225Wall TL161Whitfield JB9Zhao H270Neale BM5,6Wade TD271Heath AC2Montgomery GW9,173,272Martin NG9Sullivan PF1,7,8Kaprio J93,123Breen G3,4Gelernter J180,181,273,274Edenberg HJ182,202Bulik CM1,8,274Agrawal A2.

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.

KEYWORDS:

eating disorders; genetic correlation; substance use

PMID: 32064741