Genome wide association study identifies a novel putative mammographic density locus at 1q12-q21.

Mammographic density (MD) is an intermediate phenotype for breast cancer. Previous studies have identified genetic variants associated with MD; however, much of the genetic contribution to MD is unexplained. We conducted a two-stage genome-wide association analysis among the participants in the "Determinants of Density in Mammographies in Spain" study, together with a replication analysis in women from the Australian MD Twins and Sisters Study. Our discovery set covered a total of 3,351 Caucasian women aged 45 to 68 years, recruited from Spanish breast cancer screening centres. MD was blindly assessed by a single reader using Boyd's scale. A two-stage approach was employed, including a feature selection phase exploring 575,374 SNPs in 239 pairs of women with extreme phenotypes and a verification stage for the 183 selected SNPs in the remaining sample (2,873 women). Replication was conducted in 1,786 women aged 40 to 70 years old recruited via the Australian Twin Registry, where MD were measured using Cumulus-3.0, assessing 14 SNPs with a p value