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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.

Hunna J WatsonZeynep YilmazLaura M ThorntonChristopher HübelJonathan R I ColemanHéléna A GasparJulien BryoisAnke HinneyVirpi M LeppäManuel MattheisenSarah E MedlandStephan RipkeShuyang YaoPaola Giusti-Rodrígueznull nullKen B HanscombeKirstin L Purvesnull nullRoger A H AdanLars AlfredssonTetsuya AndoOle A AndreassenJessica H BakerWade 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 KaminskáJaakko KaprioLeila KarhunenAndreas KarwautzMartien J H KasJames L KennedyAnna Keski-RahkonenKirsty KiezebrinkYoul-Ri KimLars KlareskogKelly 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 MonteleoneMelissa A Munn-ChernoffBenedetta 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 E MitchellCatherine M OlsenJohn F PearsonNancy L PedersenMichael StroberThomas M WergeDavid C WhitemanD Blake WoodsideGarret D StuberScott D GordonJakob GroveAnjali K HendersAnders JuréusKatherine M KirkJanne T LarsenRichard ParkerLiselotte PetersenJennifer JordanMartin Alexander KennedyGrant W MontgomeryTracey D WadeAndreas BirgegårdPaul LichtensteinClaes NorringMikael LandénNicholas G MartinPreben Bo MortensenPatrick F SullivanGerome D BreenCynthia M Bulik
Published in: Nature genetics (2019)
Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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