Chen, HongjieFan, ShaoqiStone, JenniferThompson, Deborah JDouglas, JulieLi, ShuaiScott, ChristopherBolla, Manjeet KWang, QinDennis, JoeMichailidou, KyriakiLi, ChristopherPeters, UlrikeHopper, John LSouthey, Melissa CNguyen-Dumont, TuNguyen, Tuong LFasching, Peter ABehrens, AnnikaCadby, GemmaMurphy, Rachel AAronson, KristanHowell, AnthonyAstley, SusanCouch, FergusOlson, JanetMilne, Roger LGiles, Graham GHaiman, Christopher AMaskarinec, GertraudWinham, StaceyJohn, Esther MKurian, AllisonEliassen, HeatherAndrulis, IreneEvans, D GarethNewman, William GHall, PerCzene, KamilaSwerdlow, AnthonyJones, MichaelPollan-Santamaria, MarinaFernandez-Navarro, Pablo LMcConnell, Daniel SKristensen, Vessela NRothstein, Joseph HWang, PeiHabel, Laurel ASieh, WeivaDunning, Alison MPharoah, Paul D PEaston, Douglas FGierach, Gretchen LTamimi, Rulla MVachon, Celine MLindström, Sara2022-08-052022-08-052022-04-12Breast Cancer Res. 2022 Apr 12;24(1):27.http://hdl.handle.net/20.500.12105/14868Background: Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants. Methods: We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia. Results: We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p < 0.05. TWAS further identified two novel genes (SHOX2 and CRISPLD2) whose genetically predicted expression was significantly associated with MD phenotypes. Conclusions: Our findings provided novel insight into the genetic background of MD phenotypes, and further demonstrated their shared genetic basis with breast cancer.engVoRhttp://creativecommons.org/licenses/by/4.0/Breast cancerGenome-wide association study (GWAS)Mammographic densityTranscriptome-wide association study (TWAS)Breast DensityBreast NeoplasmsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPhenotypePolymorphism, Single NucleotideTranscriptomeAtribución 4.0 Internacional354141132412710.1186/s13058-022-01524-01465-542XBreast Cancer Research : BCRopen access