Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies.
Melissa A Munn-ChernoffEmma C JohnsonYi-Ling ChouJonathan R I ColemanLaura M ThorntonRaymond K WaltersZeynep YilmazJessica H BakerChristopher HübelScott GordonSarah E MedlandHunna J WatsonHéléna A GasparJulien BryoisAnke HinneyVirpi M LeppäManuel MattheisenStephan RipkeShuyang YaoPaola Giusti-RodríguezKen B HanscombeRoger A H AdanLars AlfredssonTetsuya AndoOle A AndreassenWade H BerrettiniIlka BoehmClaudette BoniVesna Boraska PericaKatharina BuehrenRoland BurghardtMatteo CassinaSven CichonMaurizio ClementiRoger D ConePhilippe CourtetScott CrowJames J CrowleyUnna N DannerOliver S P DavisMartina de ZwaanGeorge DedoussisDaniela DegortesJaniece E DeSocioDanielle M DickDimitris DikeosChristian DinaMonika Dmitrzak-WeglarzElisa DocampoLaramie E DuncanKarin EgbertsStefan EhrlichGeòrgia EscaramísTõnu EskoXavier EstivillAnne FarmerAngela FavaroFernando Fernández-ArandaManfred M FichterKrista FischerManuel FöckerLenka ForetovaAndreas J ForstnerMonica ForzanChristopher S FranklinSteven GallingerIna GieglingJohanna GiurannaFragiskos GonidakisPhilip GorwoodMonica Gratacos MayoraSébastien GuillaumeYiran GuoHakon HakonarsonKonstantinos HatzikotoulasJoanna HauserJohannes HebebrandSietske G HelderStefan HermsBeate Herpertz-DahlmannWolfgang HerzogLaura M HuckinsJames I HudsonHartmut ImgartHidetoshi InokoVladimir JanoutSusana Jiménez-MurciaAntonio JuliàGursharan KalsiDeborah KaminskáLeila KarhunenAndreas KarwautzMartien J H KasJames L KennedyAnna Keski-RahkonenKirsty KiezebrinkYoul-Ri KimKelly L KlumpGun Peggy S KnudsenMaria C La ViaStephanie Le HellardRobert D LevitanDong LiLisa LilenfeldBochao Danae LinJolanta LissowskaJurjen LuykxPierre J MagistrettiMario MajKatrin MannikSara MarsalChristian R MarshallMorten MattingsdalSara McDevittPeter McGuffinAndres MetspaluIngrid MeulenbeltNadia MicaliKaren MitchellAlessio Maria MonteleonePalmiero MonteleoneBenedetta NacmiasMarie NavratilovaIoanna NtallaJulie K O'TooleRoel A OphoffLeonid PadyukovAarno PalotieJacques PantelHana PapezovaDalila PintoRaquel RabionetAnu RaevuoriNicolas RamozTed Reichborn-KjennerudValdo RiccaSamuli RipattiFranziska RitschelMarion RobertsAlessandro RotondoDan RujescuFilip RybakowskiPaolo SantonastasoAndré ScheragStephen W SchererUlrike SchmidtNicholas J SchorkAlexandra SchosserJochen SeitzLenka SlachtovaP Eline SlagboomMargarita C T Slof-Op't LandtAgnieszka SlopienSandro SorbiBeata ŚwiątkowskaJin P SzatkiewiczIoanna TachmazidouElena TenconiAlfonso TortorellaFederica TozziJanet TreasureArtemis TsitsikaMarta Tyszkiewicz-NwaforKonstantinos TziouvasAnnemarie A van ElburgEric F van FurthGudrun WagnerEsther WaltonElisabeth WidenEleftheria ZegginiStephanie ZerwasStephan ZipfelAndrew W BergenJoseph M BodenHarry BrandtSteven CrawfordKatherine A HalmiL John HorwoodCraig JohnsonAllan S KaplanWalter H KayeJames MitchellCatherine M OlsenJohn F PearsonNancy L PedersenMichael StroberThomas WergeDavid C WhitemanD Blake WoodsideJakob GroveAnjali K HendersJanne T LarsenRichard ParkerLiselotte V PetersenJennifer JordanMartin A KennedyAndreas BirgegårdPaul LichtensteinClaes NorringMikael LandénPreben Bo MortensenRenato PolimantiJeanette N McClintickAmy E AdkinsFazil AlievSilviu-Alin BacanuAnthony BatzlerSarah BertelsenJoanna M BiernackaTim B BigdeliLi-Shiun ChenToni-Kim ClarkeFranziska DegenhardtAnna R DochertyAlexis C EdwardsJerome C FooLouis FoxJosef FrankLaura M HackAnnette M HartmannSarah M HartzStefanie Heilmann-HeimbachColin HodgkinsonPer HoffmannJouke-Jan HottengaBettina KonteJari LahtiMarius Lahti-PulkkinenDongbing LaiLannie LigthartAnu LoukolaBrion S MaherHamdi MbarekAndrew M McIntoshMatthew B McQueenJacquelyn L MeyersYuri MilaneschiTeemu PalviainenRoseann E PetersonEuijung RyuNancy L SacconeJessica E SalvatoreSandra Sanchez-RoigeMelanie SchwandtRichard ShervaFabian StreitJana StrohmaierNathaniel ThomasJen-Chyong WangBradley T WebbRobbee WedowLeah WetherillAmanda G WillsHang ZhouJason D BoardmanDanfeng ChenDoo-Sup ChoiWilliam E CopelandRobert C CulverhouseNorbert DahmenLouisa DegenhardtBenjamin W DomingueMark A FryeWolfgang GäebelCaroline HaywardMarcus IsingMargaret KeyesFalk KieferGabriele KollerJohn KramerSamuel KupermanSusanne LucaeMichael T LynskeyWolfgang MaierKarl MannSatu MännistöBertram Müller-MyhsokAlison D MurrayJohn I NurnbergerUlrich PreussKatri RäikkönenMaureen D ReynoldsMonika RidingerNorbert ScherbaumMarc A SchuckitMichael SoykaJens TreutleinStephanie H WittNorbert WodarzPeter ZillDaniel E AdkinsDorret I BoomsmaLaura J BierutSandra A BrownKathleen K BucholzE Jane CostelloHarriet de WitNancy DiazgranadosJohan G ErikssonLindsay A FarrerTatiana M ForoudNathan A GillespieAlison M GoateDavid GoldmanRichard A GruczaDana B HancockKathleen Mullan HarrisVictor HesselbrockJohn K HewittChristian J HopferWilliam G IaconoEric O JohnsonVictor M KarpyakKenneth S KendlerHenry R KranzlerKenneth KrauterPenelope A LindMatt McGueJames MacKillopPamela A F MaddenHermine H MaesPatrik K E MagnussonElliot C NelsonMarkus M NöthenAbraham A PalmerBrenda W J H PenninxBernice PorjeszJohn P RiceMarcella RietschelBrien P RileyRichard J RosePei-Hong ShenJudy SilbergMichael C StallingsRalph E TarterMichael M VanyukovScott VriezeTamara L WallJohn B WhitfieldHongyu ZhaoBenjamin M NealeTracey D WadeAndrew C HeathGrant W MontgomeryNicholas G MartinPatrick F SullivanJaakko KaprioGerome BreenJoel GelernterHoward J EdenbergCynthia M BulikArpana AgrawalPublished in: Addiction biology (2020)
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.
Keyphrases
- genome wide
- major depressive disorder
- smoking cessation
- copy number
- anorexia nervosa
- bipolar disorder
- genome wide association
- weight loss
- physical activity
- alcohol use disorder
- dna methylation
- randomized controlled trial
- artificial intelligence
- replacement therapy
- electronic health record
- hepatitis c virus
- high throughput
- big data
- hiv testing