Large-scale genotyping identifies a new locus at 22q13.2 associated with female breast size. Issue 10 (3rd July 2013)

• Record Type: Journal Article
• Authors: Li, Jingmei; Foo, Jia Nee; Schoof, Nils; Varghese, Jajini S; Fernandez-Navarro, Pablo; Gierach, Gretchen L; Quek, Swee Tian; Hartman, Mikael; Nord, Silje; Kristensen, Vessela N; Pollán, Marina; Figueroa, Jonine D; Thompson, Deborah J; Li, Yi; Khor, Chiea Chuen; Humphreys, Keith; Liu, Jianjun; Czene, Kamila; Hall, Per
• Is Part Of: Journal of medical genetics. Volume 50:Issue 10(2013)
• Page Start: 666
• Page End: 673
• Publication Date: 2013-07-03
• Subjects: Cancer: breast -- Epidemiology -- Genetic epidemiology -- Genome-wide -- Complex traits; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2013-101708
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : 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 (mm 2 ) 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.