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Shared heritability and functional enrichment across six solid cancers.

Xia JiangHilary K FinucaneFredrick R SchumacherStephanie L SchmitJonathan P TyrerYounghun HanKyriaki MichailidouCorina LesseurKaroline B KuchenbaeckerJoe G DennisDavid V ContiGraham CaseyMia M GaudetJeroen R HuygheDemetrius AlbanesMelinda C AldrichAngeline S AndrewIrene L AndrulisHoda Anton-CulverAntonis C AntoniouNatalia N AntonenkovaSusanne M ArnoldKristan J AronsonBanu K ArunElisa V BanderaRosa B BarkardottirDaniel R BarnesJyotsna BatraMatthias W BeckmannJavier BenitezSara BenllochAndrew BerchuckSonja I BerndtHeike BickeböllerStephanie A BienCarl BlomqvistStefania BocciaNatalia V BogdanovaStig Egil BojesenManjeet K BollaHiltrud B BrauchHermann BrennerJames D BrentonMark N BrookJoan BrunetHans BrunnströmDaniel D BuchananBarbara BurwinkelRalf ButzowGabriella CadoniTrinidad CaldésMaria A CaligoIan G CampbellPeter T CampbellGeraldine Cancel-TassinLisa Cannon-AlbrightDaniele CampaNeil CaporasoAndré L CarvalhoAndrew T ChanJenny Chang-ClaudeStephen J ChanockChu ChenDavid C ChristianiKathleen B M ClaesFrank ClaessensJudith ClementsJ Margriet ColléeMarcia Cruz CorreaFergus J CouchAngela CoxJulie M CunninghamCezary CybulskiKamila CzeneMary B DalyAnna deFazioPeter DevileeOrland DiezManuela Gago-DominguezJenny L DonovanThilo DörkEric J DuellAlison M DunningMiriam DwekDiana M EcclesChristopher K EdlundDigna R Velez EdwardsCarolina EllbergD Gareth EvansPeter Andreas FaschingRobert L FerrisTriantafillos LiloglouJane C FigueiredoOlivia FletcherRenée T FortnerFlorentia FostiraSilvia FranceschiEitan FriedmanSteven J GallingerPatricia A GanzJudy GarberJosé Angel García-SaenzSimon A GaytherGraham G GilesAndrew K GodwinMark S GoldbergDavid E GoldgarEllen L GoodeMarc T GoodmanGary GoodmanKjell GrankvistMark H GreeneHenrik GronbergJacek GronwaldPascal GuénelNiclas HåkanssonPer HallUte HamannFreddie C HamdyRobert J HamiltonJochen HampeAage HaugenFlorian HeitzRolando HerreroPeter HillemannsMichael HoffmeisterEstrid HøgdallYun-Chul HongJohn L HopperRichard S HoulstonPeter J HulickDavid J HunterDavid G HuntsmanGregory IdosEvgeny N ImyanitovSue Ann InglesClaudine IsaacsAnna JakubowskaPaul A JamesMark E JenkinsMattias JohanssonMikael JohanssonEsther M JohnAmit D JoshiRadka KanevaBeth Y KarlanLinda E KelemenTabea KühlKay-Tee KhawElza KhusnutdinovaAdam S KibelLambertus A KiemeneyJeri KimSusanne K KjaerJulia A KnightManolis KogevinasZsofia Kote-JaraiStella KoutrosVessela N KristensenJolanta KupryjanczykMartin LackoStephan LamDiether LambrechtsMaria Teresa LandiPhilip LazarusNhu D LeEunjung LeeFlavio LejbkowiczHeinz-Josef LenzGoska LeslieDavor LesselJenny LesterDouglas A LevineLi LiChristopher I LiAnnika LindblomNoralane M LindorGeoffrey LiuFotios LoupakisJan LubińskiLovise MaehleChristiane MaierArto MannermaaLoic Le MarchandSara MargolinTaymaa MayLesley McGuffogAlfons MeindlPooja MiddhaAustin MillerJonathan BeesleyRobert J MacInnisFrancesmary ModugnoMarco MontagnaVictor MorenoKirsten B MoysichLorelei MucciKenneth Ross MuirAnna Marie MulliganKatherine L NathansonDavid E NealAndrew R NessSusan L NeuhausenHeli NevanlinnaPolly A NewcombLisa F NewcombFinn Cilius NielsenLiene Nikitina-ZakeBørge Grønne NordestgaardRobert L NussbaumKenneth OffitEdith OlahAli Amin Al OlamaOlufunmilayo I OlopadeAndrew F OlshanHåkan OlssonAna OsorioHardev PandhaJong Y ParkNora PashayanMichael T ParsonsTanja PejovicKathryn L PenneyWilbert H M PetersCatherine M PhelanAmanda I PhippsDijana Plaseska-KaranfilskaMiranda PringDarya ProkofyevaPaolo RadiceKari StefanssonSusan J RamusLeon RaskinGadi RennertHedy S RennertElizabeth J van RensburgMarjorie J RigganHarvey A RischAngela RischMonique J RoobolBarry S RosensteinMary Anne RossingKim De RuyckEmmanouil SaloustrosDale P SandlerElinor J SawyerMatthew B SchabathJohanna SchleutkerMarjanka K SchmidtV Wendy SetiawanHongbing ShenErin M SiegelWeiva SiehChristian F SingerMartha L SlatteryKarina Dalsgaard SørensenMelissa C SoutheyAmanda B SpurdleJanet L StanfordVictoria L StevensSebastian StinzingJennifer StoneKarin SundfeldtRebecca SutphenAnthony J SwerdlowEloiza H TajaraCatherine M TangenAdonina TardónJack A TaylorM Dawn TeareManuel R TeixeiraMary Beth TerryKathryn L TerryStephen N ThibodeauMads ThomassenLine BjørgeMarc TischkowitzAmanda Ewart TolandDiana TorresPaul A TownsendRuth C TravisNadine TungShelley S TworogerCornelia M UlrichNawaid UsmaniCeline M VachonEls Van NieuwenhuysenAna VegaMiguel Elías Aguado-BarreraQin WangPenelope M WebbClarice R WeinbergStephanie WeinsteinMark C WeisslerJeffrey N WeitzelCatharine M L WestEmily WhiteAlice S WhittemoreH-Erich WichmannFredrik WiklundRobert WinqvistAlicja WolkPenella WollMichael WoodsAnna H WuXifeng WuDrakoulis YannoukakosQuan LongShanbeh ZienolddinyArgyrios ZiogasKristin K ZornJacqueline M LaneRicha SaxenaDuncan ThomasRayjean J HungBrenda DiergaardeJames McKayUlrike PetersLi HsuMontserrat García-ClosasRosalind A EelesGeorgia Chenevix-TrenchPaul J BrennanChristopher A HaimanJacques SimardDouglas F EastonStephen B GruberPaul David Peter PharoahAlkes L PriceBogdan PasaniucChristopher I AmosPeter KraftSara Lindström
Published in: Nature communications (2019)
Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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