Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci.
Authors
Chen, Hongjie
Fan, Shaoqi
Stone, Jennifer
Thompson, Deborah J
Douglas, Julie
Li, Shuai
Scott, Christopher
Bolla, Manjeet K
Wang, Qin
Dennis, Joe
Michailidou, Kyriaki
Li, Christopher
Peters, Ulrike
Hopper, John L
Southey, Melissa C
Nguyen-Dumont, Tu
Nguyen, Tuong L
Fasching, Peter A
Behrens, Annika
Cadby, Gemma
Murphy, Rachel A
Aronson, Kristan
Howell, Anthony
Astley, Susan
Couch, Fergus
Olson, Janet
Milne, Roger L
Giles, Graham G
Haiman, Christopher A
Maskarinec, Gertraud
Winham, Stacey
John, Esther M
Kurian, Allison
Eliassen, Heather
Andrulis, Irene
Evans, D Gareth
Newman, William G
Hall, Per
Czene, Kamila
Swerdlow, Anthony
Jones, Michael
Pollan, Marina
Fernandez-Navarro, Pablo
McConnell, Daniel S
Kristensen, Vessela N
NBCS Investigators
Rothstein, Joseph H
Wang, Pei
Habel, Laurel A
Sieh, Weiva
Dunning, Alison M
Pharoah, Paul DP
Easton, Douglas F
Gierach, Gretchen L
Tamimi, Rulla M
Vachon, Celine M
Publication Date
2022-04-12Journal Title
Breast Cancer Res
ISSN
1465-5411
Publisher
Springer Science and Business Media LLC
Volume
24
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Chen, H., Fan, S., Stone, J., Thompson, D. J., Douglas, J., Li, S., Scott, C., et al. (2022). Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci.. Breast Cancer Res, 24 (1) https://doi.org/10.1186/s13058-022-01524-0
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 < 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.
Keywords
Breast cancer, Mammographic Density, Genome-wide Association Study (Gwas), Transcriptome-wide Association Study (Twas), Humans, Breast Neoplasms, Genetic Predisposition to Disease, Phenotype, Polymorphism, Single Nucleotide, Female, Genome-Wide Association Study, Transcriptome, Breast Density
Sponsorship
NIH HHS (CA194393)
NCI NIH HHS (CA244670, U01 CA194393, R01 CA244670, R01 CA194393)
Identifiers
35414113, PMC9006574
External DOI: https://doi.org/10.1186/s13058-022-01524-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337173
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