title: Large-scale genotyping identifies a new locus at 22q13.2 associated with female breast size.
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.
authors.affiliation: Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Jingmei
authors.initials: J
authors.lastname: Li
authors.forename: Jia Nee
authors.initials: JN
authors.lastname: Foo
authors.forename: Nils
authors.initials: N
authors.lastname: Schoof
authors.forename: Jajini S
authors.initials: JS
authors.lastname: Varghese
authors.forename: Pablo
authors.initials: P
authors.lastname: Fernandez-Navarro
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Gierach
authors.forename: Swee Tian
authors.initials: ST
authors.lastname: Quek
authors.forename: Mikael
authors.initials: M
authors.lastname: Hartman
authors.forename: Silje
authors.initials: S
authors.lastname: Nord
authors.forename: Vessela N
authors.initials: VN
authors.lastname: Kristensen
authors.forename: Marina
authors.initials: M
authors.lastname: Pollán
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Thompson
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: Keith
authors.initials: K
authors.lastname: Humphreys
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Kamila
authors.initials: K
authors.lastname: Czene
authors.forename: Per
authors.initials: P
authors.lastname: Hall
mesh_terms: D002892:Chromosomes, Human, Pair 22; D002898:Chromosomes, Human, Pair 8; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D042361:Mammary Glands, Human / Q000254:growth & development*; D008327:Mammography; D009929:Organ Size / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
keywords: Cancer: breast; Complex traits; Epidemiology; Genetic epidemiology; Genome-wide