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

Kyriaki Michailidou, Jonathan Beesley, Sara Lindstrom, Sander Canisius, Joe Dennis, Michael Lush, Mel Maranian, Manjeet Bolla, Qin Wang, Mitul Shah, Scott Grist

    Research output: Contribution to journalArticle

    297 Citations (Scopus)

    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 â '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
    Volume47
    Issue number4
    DOIs
    Publication statusPublished - 2015

    Fingerprint Dive into the research topics of 'Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer'. Together they form a unique fingerprint.

  • Cite this

    Michailidou, K., Beesley, J., Lindstrom, S., Canisius, S., Dennis, J., Lush, M., Maranian, M., Bolla, M., Wang, Q., Shah, M., & Grist, S. (2015). Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer. Nature Genetics, 47(4), 373-380. https://doi.org/10.1038/ng.3242