Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.
Manuel A FerreiraEric R GamazonFares Al-EjehKristiina AittomäkiIrene L AndrulisHoda Anton-CulverAdalgeir ArasonVolker ArndtKristan J AronsonBanu K ArunElla AsseryanisJacopo AzzolliniJudith BalmañaDaniel R BarnesDaniel BarrowdaleMatthias W BeckmannSabine BehrensJavier BenitezMarina BermishevaKatarzyna BiałkowskaCarl BlomqvistNatalia V BogdanovaStig Egil BojesenManjeet K BollaAke BorgHiltrud BrauchHermann BrennerAnnegien BroeksBarbara BurwinkelTrinidad CaldésMaria A CaligoDaniele CampaIan G CampbellFederico CanzianJonathan CarterBrian D CarterJose E CastelaoJenny Chang-ClaudeStephen J ChanockHans ChristiansenWendy K ChungKathleen B M ClaesChristine L Clarkenull nullnull nullnull nullFergus J CouchAngela CoxSimon S CrossKamila CzeneMary B DalyMiguel de la HoyaJoe G DennisPeter DevileeOrland DiezThilo DörkAlison M DunningMiriam DwekDiana M EcclesBent EjlertsenCarolina EllbergChristoph EngelMikael ErikssonPeter Andreas FaschingOlivia FletcherHenrik FlygerEitan FriedmanDebra FrostMarike GabrielsonManuela Gago-DominguezPatricia A GanzSusan M GapsturJudy GarberMontserrat García-ClosasJosé Angel García-SaenzMia M GaudetGraham G GilesGord GlendonAndrew K GodwinMark S GoldbergDavid E GoldgarAnna González-NeiraMark H GreeneJacek GronwaldPascal GuénelChristopher A HaimanPer HallUte HamannWei HeJane HeyworthFrans B L HogervorstAntoinette HollestelleRobert N HooverJohn L HopperPeter J HulickKeith HumphreysEvgeny N Imyanitovnull nullnull nullnull nullClaudine IsaacsMilena Jakimovska ÖzdemirAnna JakubowskaPaul A JamesRamunas JanaviciusRachel C JankowitzEsther M JohnNichola JohnsonJoseph VijaiBeth Y KarlanElza KhusnutdinovaJohanna I KiiskiYon-Dschun KoMichael E JonesIrene KonstantopoulouVessela N KristensenYael LaitmanDiether LambrechtsConxi LazaroGoska LeslieJenny LesterFabienne LesueurSara LindströmJirong LongJennifer T LoudJan LubińskiEnes MakalicArto MannermaaMehdi ManoochehriSara MargolinTabea MaurerDimitrios MavroudisLesley McGuffogAlfons MeindlUsha MenonKyriaki MichailidouAustin MillerMarco MontagnaFernando MorenoLidia MoserleAnna Marie MulliganKatherine L NathansonSusan L NeuhausenHeli NevanlinnaInes NevelsteenFinn C NielsenLiene Nikitina-ZakeRobert L NussbaumKenneth OffitEdith OlahOlufunmilayo I OlopadeHåkan OlssonAna OsorioJanos PappTjoung-Won Park-SimonMichael T ParsonsInge Sokilde PedersenAna PeixotoPaolo PeterlongoPaul David Peter PharoahDijana Plaseska-KaranfilskaBruce PoppeNadege PresneauPaolo RadiceJohanna RantalaGadi RennertHarvey A RischEmmanouil SaloustrosKristin SandenElinor J SawyerMarjanka K SchmidtRita K SchmutzlerPriyanka SharmaXiao-Ou ShuJacques SimardChristian F SingerPenny SoucyMelissa C SoutheyJohn J SpinelliAmanda B SpurdleJennifer StoneAnthony J SwerdlowWilliam J TapperJack A TaylorManuel R TeixeiraMary Beth TerryAlex TeuléMads ThomassenKathrin ThöneDarcy L ThullMarc TischkowitzAmanda Ewart TolandDiana TorresThérèse TruongNadine TungCeline M VachonChristi J van AsperenAns M W van den OuwelandElizabeth J van RensburgAna VegaAlessandra VielQin WangBarbara WappenschmidtJeffrey N WeitzelCamilla WendtRobert WinqvistXiaohong R YangDrakoulis YannoukakosArgyrios ZiogasPeter KraftAntonis C AntoniouWei ZhengDouglas F EastonRoger L MilneJonathan BeesleyGeorgia Chenevix-TrenchPublished in: Nature communications (2019)
Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
Keyphrases
- breast cancer risk
- genome wide association
- genome wide
- gene expression
- copy number
- estrogen receptor
- dna methylation
- adipose tissue
- genome wide identification
- genome wide association study
- poor prognosis
- high resolution
- insulin resistance
- genome wide analysis
- type diabetes
- metabolic syndrome
- mass spectrometry
- endoplasmic reticulum