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

K Michailidou, J Beesley, S Lindstrom, S Canisius, J Dennis, MJ Lush, MJ Maranian, MK Bolla, Q (Qing) Wang, M Shah, BJ Perkins, K Czene, M Eriksson, H Darabi, JS Brand, SE Bojesen, BG Nordestgaard, H Flyger, SF Nielsen, N RahmanC Turnbull, O Fletcher, J Peto, L Gibson, I dos-Santos-Silva, J Chang-Claude, D Flesch-Janys, A Rudolph, U Eilber, S Behrens, H Nevanlinna, TA Muranen, K Aittomaki, C Blomqvist, Salima Khan, K Aaltonen, H Ahsan, MG Kibriya, AS Whittemore, EM John, KE Malone, MD Gammon, RM Santella, G Ursin, E Makalic, DF Schmidt, G Casey, DJ Hunter, SM Gapstur, MM Gaudet, WR Diver, CA Haiman, F Schumacher, BE Henderson, L Le Marchand, CD Berg, SJ Chanock, J Figueroa, RN Hoover, D Lambrechts, P Neven, H Wildiers, E van Limbergen, MK (Marjanka) Schmidt, A Broeks, S Verhoef, S Cornelissen, FJ Couch, JE Olson, E Hallberg, C Vachon, Q Waisfisz, H Meijers-Heijboer, MA (Muriel) Adank, RB van der Luijt, JM Li, JJ Liu, K Humphreys, D Kang, JY Choi, SK Park, KY Yoo, K Matsuo, H Ito, H Iwata, K Tajima, P Guenel, T Truong, C Mulot, M Sanchez, B Burwinkel, F Marme, H Surowy, C Sohn, AH Wu, CC Tseng, D van den Berg, DO Stram, A Gonzalez-Neira, J Benitez, MP Zamora, JIA Perez, XO Shu, W Lu, YT Gao, H Cai, A Cox, SS Cross, MWR Reed, IL Andrulis, JA Knight, G Glendon, AM Mulligan, EJ Sawyer, I Tomlinson, MJ Kerin, N Miller, A Lindblom, S Margolin, SH Teo, CH Yip, NAM Taib, GH Tan, Maartje Hooning, Antoinette Hollestelle, John Martens, Margriet Collee, W Blot, LB Signorello, QY Cai, JL Hopper, MC Southey, H Tsimiklis, C Apicella, CY Shen, CN Hsiung, PE Wu, MF Hou, VN Kristensen, S Nord, GIG Alnaes, GG Giles, RL Milne, C McLean, F Canzian, D Trichopoulos, P Peeters, E Lund, M Sund, KT Khaw, MJ Gunter, D Palli, LM Mortensen, L Dossus, JM Huerta, A Meindl, RK Schmutzler, C Sutter, R Yang, K Muir, A Lophatananon, S Stewart-Brown, P Siriwanarangsan, M Hartman, H Miao, KS Chia, CW Chan, PA Fasching, A Hein, MW Beckmann, L Haeberle, H Brenner, AK Dieffenbach, V Arndt, C Stegmaier, A Ashworth, N Orr, MJ Schoemaker, AJ Swerdlow, L Brinton, M Garcia-Closas, W Zheng, SL Halverson, M Shrubsole, J Long, MS Goldberg, F Labreche, M Dumont, R Winqvist, K Pylkas, A Jukkola-Vuorinen, M Grip, H Brauch, U Hamann, T Bruning, P Radice, P Peterlongo, S Manoukian, L Bernard, NV Bogdanova, T Dork, A Mannermaa, V Kataja, VM Kosma, JM Hartikainen, P Devilee, RAEM Tollenaar, Caroline Seynaeve, CJ van Asperen, A Jakubowska, J Lubinski, K Jaworska, T Huzarski, S Sangrajrang, V Gaborieau, P Brennan, J Mckay, S Slager, AE Toland, CB Ambrosone, D Yannoukakos, M Kabisch, D Torres, SL Neuhausen, H Anton-Culver, C Luccarini, C Baynes, S (Shahana) Ahmed, CS Healey, DC Tessier, D Vincent, F Bacot, G Pita, MR Alonso, N Alvarez, D Herrero, J Simard, PPDP Pharoah, P Kraft, AM Dunning, G Chenevix-Trench, P Hall, DF Easton

Research output: Contribution to journalArticleAcademicpeer-review

443 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 similar to 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 x 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 languageUndefined/Unknown
Pages (from-to)373-U127
JournalNature Genetics
Volume47
Issue number4
DOIs
Publication statusPublished - 2015

Research programs

  • EMC MGC-02-96-01
  • EMC MM-03-86-01

Cite this