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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Article scientifique 2016 Anglais

Résumé

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

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Gusev, A., Shi, H., Kichaev, G., Pomerantz, M. M., Li, F., Long, H. W., Ingles, S. A., Kittles, R. A., Strom, S. S., Rybicki, B. A., Nemesure, B., Isaacs, W. B., Zheng, W., Pettaway, C. A., Yeboah, E. D., Tettey, Y., Biritwum, R., Adjei, A. A., Tay, E., Truelove, A., Niwa, S., Chokkalingam, A. P., John, E. M., Murphy, A. B., Signorello, L. B., Carpten, J. D., Leske, M. C., Wu, S.-Y., Hennis, A. J. M., Neslund‐Dudas, C., Hsing, A. W., Chu, L. W., Goodman, P. J., Klein, E. A., Witte, J. S., Casey, G., Kaggwa, S., Cook, M. B., Stram, D. O., Blot, W. J., Eeles, R. A., Easton, D. F., Kote‐Jarai, Z., Olama, A. A. A., Benlloch, S., Muir, K., Giles, G. G., Southey, M. C., FitzGerald, L. M., Grönberg, H., Wiklund, F., Aly, M., Henderson, B. E., Schleutker, J., Wahlfors, T., Tammela, T. L., Nordestgaard, B. G., Key, T., Travis, R. C., Neal, D. E., Donovan, J., Hamdy, F. C., Pharoah, P. D., Pashayan, N., Khaw, K., Stanford, J. L., Thibodeau, S. N., McDonnell, S. K., Schaid, D. J., Maier, C., Vogel, W., Luedeke, M., Herkommer, K., Kibel, A. S., Cybulski, C., Wokołorczyk, D., Kluźniak, W., Cannon‐Albright, L., Teerlink, C. C., Brenner, H., Dieffenbach, A. K., Arndt, V., Park, J. Y., Sellers, T. A., Lin, H., Slavov, C., Kaneva, R., Mitev, V., Batra, J., Spurdle, A. B., Clements, J. A., Teixeira, M. R., Pandha, H., Michael, A., Paulo, P., Maia, S., Kierzek, A., Cook, M., Guy, M., & Govindasami, K. (2016). Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation. https://doi.org/10.1038/ncomms10979

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Auteur(s)

Alexander Gusev Huwenbo Shi Gleb Kichaev Mark M. Pomerantz Fugen Li Henry W. Long Sue A. Ingles Rick A. Kittles Sara S. Strom Benjamin A. Rybicki Barbara Nemesure William B. Isaacs Wei Zheng Curtis A. Pettaway Edward D. Yeboah Yao Tettey Richard Biritwum Andrew A. Adjei Evelyn Tay Ann Truelove Shelley Niwa Anand P. Chokkalingam Esther M. John Adam B. Murphy Lisa B. Signorello John D. Carpten M. Cristina Leske Suh-Yuh Wu Anslem J. M. Hennis Christine Neslund‐Dudas Ann W. Hsing Lisa W. Chu Phyllis J. Goodman Eric A. Klein John S. Witte Graham Casey Sam Kaggwa Michael B. Cook Daniel O. Stram William J. Blot Rosalind A. Eeles Douglas F. Easton Zsofia Kote‐Jarai Ali Amin Al Olama Sara Benlloch Kenneth Muir Graham G. Giles Melissa C. Southey Liesel M. FitzGerald Henrik Grönberg Fredrik Wiklund Markus Aly Brian E. Henderson Johanna Schleutker Tiina Wahlfors Teuvo L.J. Tammela Børge G. Nordestgaard Tim Key Ruth C. Travis David E. Neal Jenny Donovan Freddie C. Hamdy Paul D.P. Pharoah Nora Pashayan Kay‐Tee Khaw Janet L. Stanford Stephen N. Thibodeau Shannon K. McDonnell Daniel J. Schaid Christiane Maier Walther Vogel Manuel Luedeke Kathleen Herkommer Adam S. Kibel Cezary Cybulski Dominika Wokołorczyk Wojciech Kluźniak Lisa Cannon‐Albright Craig C. Teerlink Hermann Brenner Aida Karina Dieffenbach Volker Arndt Jong Y. Park Thomas A. Sellers Hui‐Yi Lin Chavdar Slavov Radka Kaneva Vanio Mitev Jyotsna Batra Amanda B. Spurdle Judith A. Clements Manuel R. Teixeira Hardev Pandha Agnieszka Michael Paula Paulo Sofia Maia Andrzej Kierzek Margaret Cook Michelle Guy Koveela Govindasami

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