Identification of a novel percent mammographic density locus at 12q24

Kristen N. Stevens, Sara Lindstrom, Christopher G. Scott, Deborah Thompson, Thomas A. Sellers, Xianshu Wang, Alice Wang, Elizabeth Atkinson, David N. Rider, Jeanette E. Eckel-passow, Jajini S. Varghese, Tina Audley, Judith Brown, Jean Leyland, Robert N. Luben, Ruth M.L. Warren, Ruth J.F. Loos, Nicholas J. Wareham, Jingmei Li, Per HallJianjun Liu, Louise Eriksson, Kamila Czene, Janet E. Olson, V. Shane pankratz, Zachary Fredericksen, Robert B. Diasio, Adam M. Lee, John A. Heit, Mariza Deandrade, Ellen L. Goode, Robert A. Vierkant, Julie M. Cunningham, Sebastian M. Armasu, Richard Weinshilboum, Brooke L. Fridley, Anthony Batzler, James N. Ingle, Norman F. Boyd, Andrew D. Paterson, Johanna Rommens, Lisa J. Martin, John L. Hopper, Melissa C. Southey, Jennifer Stone, Carmel Apicella, Peter Kraft, Susan E. Hankinson, Aditi Hazra, David J. Hunter, Douglas F. Easton, Fergus J. Couch, Rulla M. Tamimi, Celine M. Vachon

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Percent mammographic density adjusted for age and body mass index (BMI) is one of the strongest risk factors for breast cancer and has a heritable component that remains largely unidentified. We performed a three-stage genome-wide association study (GWAS) of percent mammographic density to identify novel genetic loci associated with this trait. In stage 1, we combined three GWASs of percent density comprised of 1241 women from studies at the Mayo Clinic and identified the top 48 loci (99 single nucleotide polymorphisms). We attempted replication of these loci in 7018 women from seven additional studies (stage 2). The meta-analysis of stage 1 and 2 data identified a novel locus, rs1265507 on 12q24, associated with percent density, adjusting for age and BMI (P = 4.43 × 10-8). We refined the 12q24 locus with 459 additional variants (stage 3) in a combined analysis of all three stages (n = 10 377) and confirmed that rs1265507 has the strongest association in the 12q24 region (P = 1.03 × 10-8). Rs1265507 is located between the genes TBX5 and TBX3, which are members of the phylogenetically conserved T-box gene family and encode transcription factors involved in developmental regulation. Understanding the mechanism underlying this association will provide insight into the genetics of breast tissue composition.

Original languageEnglish (US)
Article numberdds158
Pages (from-to)3299-3305
Number of pages7
JournalHuman molecular genetics
Issue number14
StatePublished - Jul 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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