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

kConFab investigators, AOCS Group, NBCS, GENICA Network, Kyriaki Michailidou, Jonathan Beesley, Sara Lindstrom, Sander Canisius, Joe Dennis, Michael J Lush, Mel J Maranian, Manjeet K Bolla, Qin Wang, Mitul Shah, Barbara J Perkins, Kamila Czene, Mikael Eriksson, Hatef Darabi, Judith S Brand, Stig E BojesenBørge G Nordestgaard, Henrik Flyger, Sune F Nielsen, Nazneen Rahman, Clare Turnbull, BOCS, Olivia Fletcher, Julian Peto, Lorna Gibson, Isabel dos-Santos-Silva, Jenny Chang-Claude, Dieter Flesch-Janys, Anja Rudolph, Ursula Eilber, Sabine Behrens, Heli Nevanlinna, Taru A Muranen, Kristiina Aittomäki, Carl Blomqvist, Sofia Khan, Kirsimari Aaltonen, Habibul Ahsan, Muhammad G Kibriya, Alice S Whittemore, Esther M John, Kathleen E Malone, Marilie D Gammon, Regina M Santella, Giske Ursin, Enes Makalic, Daniel F Schmidt, Graham Casey, David J Hunter, Susan M Gapstur, Jonine Figueroa, Ian Tomlinson

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)373-380
Number of pages8
JournalNature Genetics
Issue number4
Early online date9 Mar 2015
Publication statusPublished - Apr 2015

Keywords / Materials (for Non-textual outputs)

  • Breast Neoplasms
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Meta-Analysis as Topic
  • Microarray Analysis
  • Polymorphism, Single Nucleotide


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