Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 04 2019
15 04 2019
Historique:
received:
18
05
2018
accepted:
14
12
2018
entrez:
17
4
2019
pubmed:
17
4
2019
medline:
17
5
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30988301
doi: 10.1038/s41467-018-08053-5
pii: 10.1038/s41467-018-08053-5
pmc: PMC6465407
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1741Subventions
Organisme : NCI NIH HHS
ID : U10 CA180868
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : Cancer Research UK
ID : 11174
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233191
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_14105
Pays : United Kingdom
Investigateurs
Julian Adlard
(J)
Munaza Ahmed
(M)
Julian Barwell
(J)
Angela Brady
(A)
Carole Brewer
(C)
Jackie Cook
(J)
Rosemarie Davidson
(R)
Alan Donaldson
(A)
Jacqueline Eason
(J)
Ros Eeles
(R)
D Gareth Evans
(DG)
Helen Gregory
(H)
Helen Hanson
(H)
Alex Henderson
(A)
Shirley Hodgson
(S)
Louise Izatt
(L)
M John Kennedy
(MJ)
Fiona Lalloo
(F)
Clare Miller
(C)
Patrick J Morrison
(PJ)
Kai-Ren Ong
(KR)
Jo Perkins
(J)
Mary E Porteous
(ME)
Mark T Rogers
(MT)
Lucy E Side
(LE)
Katie Snape
(K)
Lisa Walker
(L)
Patricia A Harrington
(PA)
Norbert Arnold
(N)
Bernd Auber
(B)
Nadja Bogdanova-Markov
(N)
Julika Borde
(J)
Almuth Caliebe
(A)
Nina Ditsch
(N)
Bernd Dworniczak
(B)
Stefanie Engert
(S)
Ulrike Faust
(U)
Andrea Gehrig
(A)
Eric Hahnen
(E)
Jan Hauke
(J)
Julia Hentschel
(J)
Natalie Herold
(N)
Ellen Honisch
(E)
Walter Just
(W)
Karin Kast
(K)
Mirjam Larsen
(M)
Johannes Lemke
(J)
Huu Phuc Nguyen
(HP)
Dieter Niederacher
(D)
Claus-Eric Ott
(CE)
Konrad Platzer
(K)
Esther Pohl-Rescigno
(E)
Juliane Ramser
(J)
Kerstin Rhiem
(K)
Doris Steinemann
(D)
Christian Sutter
(C)
Raymonda Varon-Mateeva
(R)
Shan Wang-Gohrke
(S)
Bernhard H F Weber
(BHF)
Fabienne Prieur
(F)
Pascal Pujol
(P)
Charlotte Sagne
(C)
Nicolas Sevenet
(N)
Hagay Sobol
(H)
Johanna Sokolowska
(J)
Dominique Stoppa-Lyonnet
(D)
Laurence Venat-Bouvet
(L)
Rosemary Balleine
(R)
Robert Baxter
(R)
Stephen Braye
(S)
Jane Carpenter
(J)
Jane Dahlstrom
(J)
John Forbes
(J)
Soon C Lee
(SC)
Deborah Marsh
(D)
Adrienne Morey
(A)
Nirmala Pathmanathan
(N)
Peter Simpson
(P)
Allan Spigelman
(A)
Nicholas Wilcken
(N)
Desmond Yip
(D)
Bernadette A M Heemskerk-Gerritsen
(BAM)
Matti A Rookus
(MA)
Caroline M Seynaeve
(CM)
Frederieke H van der Baan
(FH)
Annemieke H van der Hout
(AH)
Lizet E van der Kolk
(LE)
Rob B van der Luijt
(RB)
Carolien H M van Deurzen
(CHM)
Helena C van Doorn
(HC)
Klaartje van Engelen
(K)
Liselotte van Hest
(L)
Theo A M van Os
(TAM)
Senno Verhoef
(S)
Maartje J Vogel
(MJ)
Juul T Wijnen
(JT)
Alexander Miron
(A)
Miroslav Kapuscinski
(M)
Anita Bane
(A)
Eric Ross
(E)
Saundra S Buys
(SS)
Thomas A Conner
(TA)
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