biostudies-literatureKarlsson Linner REconomic and Social Research CouncilNICHD NIH HHSCancer Research UKNIA NIH HHSMedical Research CouncilNational Institute for Health Research (NIHR)NNF Center for Basic Metabolic ResearchLundbeck FoundationWellcome TrustNovo Nordisk FondenBiotechnology and Biological Sciences Research Council245-257https://www.ebi.ac.uk/biostudies/studies/S-EPMC6713272biostudies-literatureUnknown51(2)Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated ([Formula: see text] ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with geneNature geneticsGenome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences.PMC6713272P30 AG012810R01 AG0158191811434Pers GroupNF-SI-0507-10228R190-2014-390410119R56 AG042568R01 AG042568NIHR-RP-R3-12-013G0600237P01 AG005842T32 AG000186P01 HD031921ES/S008349/1NNF16OC00214961805084MR/N01104X/1G0901461MR/N01104X/2R01 AG033678MC_UU_00007/10BB/F019394/1G0700704B213422/Z/18/ZP30 AG010161208806/Z/17/ZMR/K026992/1P2C HD066613MC_UU_12013/4ES/N00812X/1ES/M008592/1R03 HD097630BB/F022441/1NF-SI-0514-10027G1001799R01 AG017917G0100594McQueen MBLebreton MPHarris KMUitterlinden AGVerweij NAlves IMiller MBTonjes AFontana MALatvala AWedow RHolliday EGPendleton NWeir DRMilani LPoot RAGandin IRobino ATiemeier HStrauch KScott RJFrayling TBerger KPenninx BCesarini DKronberg-Guzman JThorsteinsdottir UGunnarsson BVaccargiu SFontanillas PConcas MPZhu ZHuffman JEWhite JGratten JRipatti SVosa UEmilsson VAuton ASmith AVLaibson DMeurs JVTian CVerlouw JDemuth IRaikkonen KSmith BHBrandsma JHVolker UMilaneschi YElson SLBaumbach Cde Vlaming RWellmann JHuber KEFaul JDOldmeadow CCusi DBoardman JDLoukola APerola MSalvi EEvans DMWilson JFGasparini PMedland SELee JJTimshel PKirsten HInternational Cannabis ConsortiumMarques-Vidal PGieger CMagi RMcCreight JCKahonen MEriksson JGJarvelin MRAndiappan ASchunk DGonzalez JRKarhunen VSullivan PJockel KHLiu TDerringer JShelton JFKalafati IPNauck MLind PAIacono WGScholz MMontgomery GWSeppala IHomuth GRueger SBeauchamp JPPervjakova NClark DWLauner LJHypponen ERing SMVolzke HLaibson DIBiino GLevinson DFHarris SEGejman PVMeyer MNHoffmann WVisscher PMPeyrot WJBattle AHasler GMagnusson PKESathirapongsasuti JFStaessen JAChen GBHarris TBPetrovic KETurley PBuzdugan LFehr EKeltigangas-Jarvinen LFranke LKraja ATVacic VRueedi RFranke BHinds DADeloukas PKong AHofman AHeijmans BKukushkina VKanoni SSaha ATong LTaskesen EKong ESanchez-Roige SLiewald DCMAgbessi MBennett DAPers THJansen RKaakinen MASchmidt BProkisch HSchmidt HMeddens SFWSchmidt RMarten JMeitinger T23and Me Research TeamBacelis Jde Jager PLPorteous DJSchramm KDuijn CMVOllier WERAbdellaoui ARooij FJVLitterman NKBenjamin DJMcGue MKutalik ZOskarsson SHofer EHalldorsson BVDolan CCSocial Science Genetic Association ConsortiumKrueger RFMihailov ELehrer SFAlipanahi BMcIntyre MHKoskinen SKovacs PGalesloot TERudan IMountain JLVitart VWaage JThurik ARKumari MBiroli PPsaty BMPickrell JKKaprio JKardia SLRMartin NGSarin APNorthover CAMOkbay ANivard MGPierce BLebreton MGrabe HJJain SEsko TLill CMHoran MATrzaskowski MGirotto GZeng BMarioni REBryc KGibson GUrsano RJLevin RZStein MBKiemeney LALMZhao WZund CLVonk JMAhsan HTimpson NJJohannesson MNyholt DRThom KMcMahon GQuaye LGupta RJan Bonder MKettunen JEisele LVlaming RVozzi DMyhre RBertram LBisgaard HKooyman MVollenweider PPourcain BSAlizadeh BZTung JYRustichini ADeelen PKasela SThorleifsson GVinkhuyzen AAEChen CYMacKillop JCappuccio FPAhluwalia TSFurlotte NALahti JMost PJVSutter MWillemsen GHeath ACMeisinger CMarigorta UMRostapshova OEibich PSamani NJKarlsson Linner ReQTLgen ConsortiumKaasik KMuller-Nurasyid MHall LMBjornsdottir GYaghootkar HSchraut KEFeitosa MFWestra HJChristiansen MMannikko MForstner AJAgee MMangino MTimshel PNNavarro ALoeffler MHottenga JJSazonova OVMetspalu ASvento RKalnapenkis AVenturini CHarst PVClaringbould ALindgren KOPalmer AALee SJVZhang FShringarpure SUlivi SProvince MAHocking LJKoellinger PDGudnason VAttia JRBakshi APirastu MPalotie APirastu NDeary IJIkram MABeutner FBonnelykke KJugessur ACucca FHayward CMadden PAAwadalla PWagner GGGharib SARaitakari ONelson CPPosthuma DKrohn KSteinhagen-Thiessen EFischbacher UChabris CFSorensen TIAHammerschlag ARBaumeister SEVuckovic DWare EBDavies GThiery JTobin MDBorecki IBAmin NSalomaa VDedoussis GVGroenen PJFLee BPaternoster LPowell JKessler RCPedersen NLSmith JATino SPSmart MCBoomsma DIEklund NTerracciano ARing SCaplin AHQian YSchmidt KMTeumer AKim YShi JKarlsson RDe Neve JEKolcic IStefansson KPayton ASanders ARBell RKWit HStumvoll MFave MJBultmann USpector TDJoshi PKWu YMeddens GARotzchke OYang JWilson CHHemani GWright AFPitts SJMorcillo-Suarez CRietveld CAMaki-Opas THorikoshi MBoyle PAKroh MDongen JVPolasek OConlin ADing JPower CJacobsson BSchlessinger DMuntane Gde Leeuw CLehtimaki TBao YLichtenstein PConley DCTimmers PRHJCampbell HLichtner PSmith GDKleinman AHoen PTfalseGenome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences.Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated ([Formula: see text] ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with gene2019-01-01T00:00:00Z2019 Feb2026-05-01T03:50:15.289Z2019-09-05T07:02:33ZS-EPMC67132723064325810.1038/s41588-018-0309-3