Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
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Authors
Chen, H.Fan, S.
Stone, J.
Thompson, D. J.
Douglas, J.
Li, S.
Scott, C.
Bolla, M. K.
Wang, Q.
Dennis, J.
Michailidou, K.
Li, C.
Peters, U.
Hopper, J. L.
Southey, M. C.
Nguyen-Dumont, T.
Nguyen, T. L.
Fasching, P. A.
Behrens, A.
Cadby, G.
Murphy, R. A.
Aronson, K.
Howell, Anthony
Astley, S.
Couch, F.
Olson, J.
Milne, R. L.
Giles, G. G.
Haiman, C. A.
Maskarinec, G.
Winham, S.
John, E. M.
Kurian, A.
Eliassen, H.
Andrulis, I.
Evans, D. G.
Newman, W. G.
Hall, P.
Czene, K.
Swerdlow, A.
Jones, M.
Pollan, M.
Fernandez-Navarro, P.
McConnell, D. S.
Kristensen, V. N.
Rothstein, J. H.
Wang, P.
Habel, L. A.
Sieh, W.
Dunning, A. M.
Pharoah, P. D. P.
Easton, D. F.
Gierach, G. L.
Tamimi, R. M.
Vachon, C. M.
Lindström, S.
Affiliation
Department of Epidemiology, School of Public Health, University of Washington, 3980 15th Ave NE, Box 351619, Seattle, WA, 98195, USAIssue Date
2022
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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.Citation
Chen H, Fan S, Stone J, Thompson DJ, Douglas J, Li S, et al. Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci. Vol. 24, Breast Cancer Research. Springer Science and Business Media LLC; 2022.Journal
Breast Cancer ResearchDOI
10.1186/s13058-022-01524-0PubMed ID
35414113Additional Links
https://dx.doi.org/10.1186/s13058-022-01524-0Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1186/s13058-022-01524-0