학술논문
Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
Document Type
article
Author
Hongjie Chen; Shaoqi Fan; Jennifer Stone; Deborah J. Thompson; Julie Douglas; Shuai Li; Christopher Scott; Manjeet K. Bolla; Qin Wang; Joe Dennis; Kyriaki Michailidou; Christopher Li; Ulrike Peters; John L. Hopper; Melissa C. Southey; Tu Nguyen-Dumont; Tuong L. Nguyen; Peter A. Fasching; Annika Behrens; Gemma Cadby; Rachel A. Murphy; Kristan Aronson; Anthony Howell; Susan Astley; Fergus Couch; Janet Olson; Roger L. Milne; Graham G. Giles; Christopher A. Haiman; Gertraud Maskarinec; Stacey Winham; Esther M. John; Allison Kurian; Heather Eliassen; Irene Andrulis; D. Gareth Evans; William G. Newman; Per Hall; Kamila Czene; Anthony Swerdlow; Michael Jones; Marina Pollan; Pablo Fernandez-Navarro; Daniel S. McConnell; Vessela N. Kristensen; NBCS Investigators; Joseph H. Rothstein; Pei Wang; Laurel A. Habel; Weiva Sieh; Alison M. Dunning; Paul D. P. Pharoah; Douglas F. Easton; Gretchen L. Gierach; Rulla M. Tamimi; Celine M. Vachon; Sara Lindström
Source
Breast Cancer Research, Vol 24, Iss 1, Pp 1-15 (2022)
Subject
Language
English
ISSN
1465-542X
Abstract
Abstract Background 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