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Large-scale genotyping identifies a new locus at 22q13.2 associated with female breast size
  1. Jingmei Li1,
  2. Jia Nee Foo1,
  3. Nils Schoof2,
  4. Jajini S Varghese3,4,
  5. Pablo Fernandez-Navarro5,6,
  6. Gretchen L Gierach7,
  7. Swee Tian Quek8,
  8. Mikael Hartman9,10,
  9. Silje Nord11,
  10. Vessela N Kristensen11,12,
  11. Marina Pollán5,6,
  12. Jonine D Figueroa7,
  13. Deborah J Thompson3,
  14. Yi Li1,
  15. Chiea Chuen Khor1,
  16. Keith Humphreys2,
  17. Jianjun Liu1,9,10,
  18. Kamila Czene2,
  19. Per Hall2
  1. 1Human Genetics, Genome Institute of Singapore, Singapore, Singapore
  2. 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  3. 3Centre for Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  4. 4Plastic Surgery Unit, Royal Free Hospital, London, UK
  5. 5Cancer and Environmental Epidemiology Unit, National Centre for Epidemiology, Carlos III Institute of Health, Madrid, Spain
  6. 6Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública—CIBERESP), Spain
  7. 7Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  8. 8Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  9. 9Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
  10. 10Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  11. 11Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway
  12. 12Department of Clinical Molecular Biology, Division of Medicine, Akershus University Hospital, Ahus, Norway
  1. Correspondence to Per Hall, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, Stockholm 171 77, Sweden; Per.Hall{at}


Background Individual differences in breast size are a conspicuous feature of variation in human females and have been associated with fecundity and advantage in selection of mates. To identify common variants that are associated with breast size, we conducted a large-scale genotyping association meta-analysis in 7169 women of European descent across three independent sample collections with digital or screen film mammograms.

Methods The samples consisted of the Swedish KARMA, LIBRO-1 and SASBAC studies genotyped on iCOGS, a custom illumina iSelect genotyping array comprising of 211 155 single nucleotide polymorphisms (SNPs) designed for replication and fine mapping of common and rare variants with relevance to breast, ovary and prostate cancer. Breast size of each subject was ascertained by measuring total breast area (mm2) on a mammogram.

Results We confirm genome-wide significant associations at 8p11.23 (rs10086016, p=1.3×10−14) and report a new locus at 22q13 (rs5995871, p=3.2×10−8). The latter region contains the MKL1 gene, which has been shown to impact endogenous oestrogen receptor α transcriptional activity and is recruited on oestradiol sensitive genes. We also replicated previous genome-wide association study findings for breast size at four other loci.

Conclusions A new locus at 22q13 may be associated with female breast size.

  • Cancer: breast
  • Epidemiology
  • Genetic epidemiology
  • Genome-wide
  • Complex traits

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