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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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  • 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 Bojesen
  • Børge G Nordestgaard
  • Henrik Flyger
  • Sune F Nielsen
  • Nazneen Rahman
  • Clare Turnbull
  • 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
  • Mia M Gaudet
  • BOCS
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind47
Udgave nummer4
Sider (fra-til)373-80
Antal sider8
ISSN1061-4036
DOI
StatusUdgivet - apr. 2015

ID: 45699475