Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
BioMed Central (BMC), 2022
Online
academicJournal
Zugriff:
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. ; This work was supported by CA244670 and CA194393. European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and the PERSPECTIVE I&I project, funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministère de l’Économie et de l'Innovation du Québec through Genome Québec, the Quebec Breast Cancer Foundation. The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Additional funding for BCAC is provided via the Confluence project which is funded with intramural funds from the National Cancer Institute Intramural Research Program, National Institutes of Health. Genotyping of the OncoArray was funded by the NIH ...
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Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
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| Autor/in / Beteiligte Person: | 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-Santamaria, Marina ; Fernandez-Navarro, Pablo L ; McConnell, Daniel S ; Kristensen, Vessela N ; Rothstein, Joseph H ; Wang, Pei ; Habel, Laurel A ; Sieh, Weiva ; Dunning, Alison M ; Pharoah, Paul D P ; Easton, Douglas F ; Gierach, Gretchen L ; Tamimi, Rulla M ; Vachon, Celine M ; Lindström, Sara ; Unión Europea. Comisión Europea. H2020 ; Canadian Institutes of Health Research ; Quebec Breast Cancer Foundation ; Government of Quebec (Canadá) ; National Institutes of Health (Estados Unidos) ; Unión Europea. Comisión Europea. 7 Programa Marco ; Cancer Research UK (Reino Unido) ; Susan G. Komen Breast Cancer Foundation ; Ovarian Cancer Research Foundation (Astrualia) ; Australian Breast Cancer Family Study ; NIH - National Cancer Institute (NCI) (Estados Unidos) ; National Health and Medical Research Council (Australia) ; New South Wales Cancer Council (Reino Unido) ; Victorian Cancer Agency ; National Breast Cancer Foundation (Australia) ; Australia, Cancer ; Universitätsklinikum Erlangen (Alemania) ; Consorcio Gallego de Cáncer de Mama (BREOGAN) ; Instituto de Salud Carlos, III ; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) ; Galicia Sur Biomedical Foundation ; Xunta de Galicia (España) ; Ministerio de Sanidad, Servicios Sociales e Igualdad (España) ; Ministerio de Economía y Competitividad (España) ; Canadian Cancer Society ; NIHR - Manchester Biomedical Research Centre (Reino Unido) ; Cancer Council New South Wales (Australia) ; Cancer Council Victoria (Australia) ; Cancer Council Tasmania (Australia) ; Cancer Council South (Australia) ; Cancer Council Western Australia (Australia) ; United States Army Medical Research and Development Command ; Cancer Council Queensland (Australia) ; NIH - NCI-Specialized Programs of Research Excellence (SPORE) in Breast Cancer (Estados Unidos) ; Victorian Health Promotion Foundation ; The Research Council of Norway (Noruega) ; Southern and Eastern Norway Regional Health Authority ; Norwegian Cancer Society ; Agency for Science, Technology and Research (Singapur) ; Institute of Cancer Research (Reino Unido) |
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| Veröffentlichung: | BioMed Central (BMC), 2022 |
| Medientyp: | academicJournal |
| ISSN: | 1465-542X (print) |
| DOI: | 10.1186/s13058-022-01524-0 |
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