학술논문

A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer
Document Type
article
Author
Wu, LangShi, WeiLong, JirongGuo, XingyiMichailidou, KyriakiBeesley, JonathanBolla, Manjeet KShu, Xiao-OuLu, YingchangCai, QiuyinAl-Ejeh, FaresRozali, EsdyWang, QinDennis, JoeLi, BingshanZeng, ChenjieFeng, HelianGusev, AlexanderBarfield, Richard TAndrulis, Irene LAnton-Culver, HodaArndt, VolkerAronson, Kristan JAuer, Paul LBarrdahl, MyrtoBaynes, CarolineBeckmann, Matthias WBenitez, JavierBermisheva, MarinaBlomqvist, CarlBogdanova, Natalia VBojesen, Stig EBrauch, HiltrudBrenner, HermannBrinton, LouiseBroberg, PerBrucker, Sara YBurwinkel, BarbaraCaldés, TrinidadCanzian, FedericoCarter, Brian DCastelao, J EstebanChang-Claude, JennyChen, XiaoqingCheng, Ting-Yuan DavidChristiansen, HansClarke, Christine LNBCS CollaboratorsCollée, MargrietCornelissen, StenCouch, Fergus JCox, DavidCox, AngelaCross, Simon SCunningham, Julie MCzene, KamilaDaly, Mary BDevilee, PeterDoheny, Kimberly FDörk, Thilodos-Santos-Silva, IsabelDumont, MartineDwek, MiriamEccles, Diana MEilber, UrsulaEliassen, A HeatherEngel, ChristophEriksson, MikaelFachal, LauraFasching, Peter AFigueroa, JonineFlesch-Janys, DieterFletcher, OliviaFlyger, HenrikFritschi, LinGabrielson, MarikeGago-Dominguez, ManuelaGapstur, Susan MGarcía-Closas, MontserratGaudet, Mia MGhoussaini, MayaGiles, Graham GGoldberg, Mark SGoldgar, David EGonzález-Neira, AnnaGuénel, PascalHahnen, EricHaiman, Christopher AHåkansson, NiclasHall, PerHallberg, EmilyHamann, UteHarrington, PatriciaHein, AlexanderHicks, BelyndaHillemanns, PeterHollestelle, AntoinetteHoover, Robert NHopper, John LHuang, Guanmengqian
Source
Nature Genetics. 50(7)
Subject
Biological Sciences
Genetics
Biotechnology
Prevention
Clinical Research
Human Genome
Breast Cancer
Genetic Testing
Cancer
2.1 Biological and endogenous factors
4.1 Discovery and preclinical testing of markers and technologies
Aetiology
Detection
screening and diagnosis
Breast Neoplasms
Case-Control Studies
Female
Gene Expression
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Polymorphism
Single Nucleotide
Risk
Transcriptome
NBCS Collaborators
kConFab/AOCS Investigators
Medical and Health Sciences
Developmental Biology
Agricultural biotechnology
Bioinformatics and computational biology
Language
Abstract
The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P