Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci

Chen H, Fan S, Stone J, Thompson DJ, Douglas J, Li S, Scott C, Bolla MK, Wang Q, Dennis J, Michailidou K, Li C, Peters U, Hopper JL, Southey MC, Nguyen-Dumont T, Nguyen TL, Fasching P, Behrens A, Cadby G, Murphy RA, Aronson K, Howell A, Astley S, Couch F, Olson J, Milne RL, Giles GG, Haiman CA, Maskarinec G, Winham S, John EM, Kurian A, Eliassen H, Andrulis I, Evans DG, Newman WG, Hall P, Czene K, Swerdlow A, Jones M, Pollan M, Fernandez-Navarro P, Mcconnell DS, Kristensen VN, Rothstein JH, Wang P, Habel LA, Sieh W, Dunning AM, Pharoah PDP, Easton DF, Gierach GL, Tamimi RM, Vachon CM, Lindstrom S (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 24

Pages Range: 27-

Journal Issue: 1

DOI: 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.

Authors with CRIS profile

Involved external institutions

University of British Columbia Canada (CA) Queen's University United Kingdom (GB) University of Manchester United Kingdom (GB) Mayo Clinic United States (USA) (US) The University of Melbourne Australia (AU) University of Southern California (USC) United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) University of Washington United States (USA) (US) National Cancer Institute (NCI) United States (USA) (US) University of Western Australia (UWA) Australia (AU) University of Cambridge United Kingdom (GB) University of Michigan United States (USA) (US) The Institute of Cancer Research (ICR) United Kingdom (GB) Icahn School of Medicine at Mount Sinai United States (USA) (US) Cyprus Institute of Neurology and Genetics Cyprus (CY) Monash University Australia (AU) Kaiser Permanente United States (USA) (US) Stanford University United States (USA) (US) Harvard University United States (USA) (US) Mount Sinai Hospital (MSH) Canada (CA) Karolinska Institute Sweden (SE) Universidad Carlos III de Madrid (UC3M) Spain (ES) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Cornell University United States (USA) (US)

How to cite

APA:

Chen, H., Fan, S., Stone, J., Thompson, D.J., Douglas, J., Li, S.,... Lindstrom, S. (2022). Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci. Breast Cancer Research, 24(1), 27-. https://doi.org/10.1186/s13058-022-01524-0

MLA:

Chen, Hongjie, et al. "Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci." Breast Cancer Research 24.1 (2022): 27-.

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