Медицинская библиотека · Breast cancer research : BCR · 2022

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

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 D P, Easton Douglas F, Gierach Gretchen L, Tamimi Rulla M, Vachon Celine M, Lindström Sara

СтатьяПоддержка NIH: внешняя программаПеревод пока не подготовлен

Аннотация

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.

Для цитирования: 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 D P, Easton Douglas F, Gierach Gretchen L, Tamimi Rulla M, Vachon Celine M, Lindström Sara. Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci.. Breast cancer research : BCR. 2022. DOI: 10.1186/s13058-022-01524-0.

Предметные рубрики MeSH

Breast Density Breast Neoplasms Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Phenotype Polymorphism, Single Nucleotide Transcriptome

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