Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

Nature Genetics
Kyriaki MichailidouDouglas F Easton

Abstract

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

References

Apr 23, 2002·Nature Genetics·Hanne Meijers-HeijboerUNKNOWN CHEK2-Breast Cancer Consortium
May 4, 2004·American Journal of Human Genetics·UNKNOWN CHEK2 Breast Cancer Case-Control Consortium
May 10, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Farin KamangarWilliam F Anderson
Feb 13, 2007·Nature Genetics·Angela CoxUNKNOWN Breast Cancer Association Consortium
May 29, 2007·Nature·Douglas F EastonBruce A J Ponder
Apr 9, 2008·Nature Genetics·Daniel F GudbjartssonKari Stefansson
Mar 31, 2009·Nature Genetics·Shahana AhmedDouglas F Easton
May 11, 2010·Nature Genetics·Clare TurnbullDouglas F Easton
Jun 3, 2010·Nature Reviews. Genetics·Jonathan Marchini, Bryan Howie
Jun 29, 2010·Genetic Epidemiology·Miriam S UdlerDouglas F Easton
Jul 10, 2010·Bioinformatics·Cristen J WillerGonçalo R Abecasis
Jan 26, 2011·Journal of the National Cancer Institute·Olivia FletcherJulian Peto
Jan 24, 2012·Nature Genetics·Maya GhoussainiDouglas F Easton
Feb 15, 2012·Cancer Research·Kristen N StevensFergus J Couch
Sep 25, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Mar 29, 2013·Nature Genetics·Kyriaki MichailidouDouglas F Easton
Mar 29, 2013·Nature Genetics·Montserrat Garcia-ClosasPeter Kraft
Sep 13, 2013·Neoplasia : an International Journal for Oncology Research·Zehua WangCeshi Chen
Oct 15, 2013·Cell·Denes HniszRichard A Young
Feb 5, 2014·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Habibul AhsanAlice S Whittemore
Jan 13, 2015·Nature Genetics·Karoline B KuchenbaeckerUNKNOWN Consortium of Investigators of Modifiers of BRCA1 and BRCA2

❮ Previous
Next ❯

Citations

Jan 20, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·Paolo RadicePaolo Peterlongo
Feb 4, 2016·The New England Journal of Medicine·Lynn C Hartmann, Noralane M Lindor
Jan 21, 2016·European Journal of Human Genetics : EJHG·Amandine I GarciaSylvie Mazoyer
Jan 13, 2016·British Journal of Cancer·Anja RudolphMarjanka K Schmidt
Dec 15, 2015·American Journal of Epidemiology·Sophia S Wang, James V Lacey
Mar 24, 2016·Proceedings of the National Academy of Sciences of the United States of America·Haruna TakedaNeal G Copeland
Apr 8, 2016·Personalized Medicine·Nora PashayanMartin Widschwendter
Apr 12, 2016·Frontiers in Plant Science·Gaofeng ZhouChengdao Li
Mar 31, 2016·Genetic Epidemiology·Paul J NewcombeSylvia Richardson
Apr 6, 2016·Cancer Letters·Ivana Maleva KostovskaThilo Dörk
Apr 14, 2016·Nature Reviews. Clinical Oncology·Yiwey ShiehLaura J Esserman
Jul 28, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Andrew J LeeAntonis C Antoniou
Jul 15, 2015·Breast Cancer Research : BCR·D Gareth Evans, Anthony Howell
Jun 4, 2015·Breast Cancer Research and Treatment·Pål MøllerD Gareth Evans
Apr 27, 2016·Cell·Galina A EriksonAli Torkamani
May 3, 2016·Gastroenterology·Luis G Carvajal Carmona, Ian Tomlinson
May 14, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Hongyan LiDavid E Goldgar
Jun 9, 2016·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Masanobu TakahashiChikashi Ishioka
Jul 28, 2016·American Journal of Public Health·Graham A ColditzSusan E Hankinson
Jul 28, 2016·American Journal of Public Health·Megan S RiceRulla M Tamimi
Aug 6, 2016·Critical Reviews in Biochemistry and Molecular Biology·Guido KeijzersLene Juel Rasmussen
Aug 28, 2016·Breast Cancer Research and Treatment·Yiwey ShiehElad Ziv
Aug 31, 2016·Breast Cancer Research and Treatment·Minggui XuBo Zhang
Aug 17, 2016·Endocrine-related Cancer·Roger L Milne, Antonis C Antoniou
Sep 27, 2016·International Journal of Cancer. Journal International Du Cancer·Juncheng DaiHongbing Shen
Oct 27, 2016·European Journal of Human Genetics : EJHG·Kirsi MäättäJohanna Schleutker
Oct 19, 2016·Clinical Genetics·B BorgheseD Vaiman
Dec 29, 2016·European Journal of Human Genetics : EJHG·Roberto Puzone, Ulrich Pfeffer
May 7, 2016·PloS One·Liisa M PelttariHeli Nevanlinna
Nov 3, 2016·PloS One·Yoo-Jeong HanOlufunmilayo I Olopade

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping
ChIP-Seq

Software Mentioned

SNPTEST
METAL
Minimac
Galaxy
iCOGS
SHAPEIT
MACH
UCSC Table browser
IMPUTEv2

Related Concepts