Shared heritability and functional enrichment across six solid cancers

著者: Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline Kuchenbaecker, Joe Dennis, David V. Conti, Graham Casey, Mia M. Gaudet, Jeroen R. Huyghe, Demetrius Albanes, Melinda C. Aldrich, Angeline S. Andrew, Irene L. Andrulis, Hoda Anton‐Culver, Antonis C. Antoniou, Natalia Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu Arun, Elisa V. Bandera, Rósa B. Barkardóttir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benı́tez, Sara Benlloch, Andrew Berchuck, Sonja I. Berndt, Heike Bickeböller, Stephanie A. Bien, Carl Blomqvist, Stefania Boccia, Natalia Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, James D. Brenton, Mark N. Brook, Joan Brunet, Hans Brunnström, Daniel D. Buchanan, Barbara Burwinkel, Ralf Bützow, Gabriella Cadoni, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Peter T. Campbell, Géraldine Cancel‐Tassin, Lisa Cannon‐Albright, Daniele Campa, Neil E. Caporaso, André Lopes Carvalho, Andrew T. Chan, Jenny Chang‐Claude, Stephen J. Chanock, Chu Chen, David C. Christiani, Kathleen Claes, Frank Claessens, Judith A. Clements, J. Margriet Collée, Marcia Cruz Correa, Fergus J. Couch, Angela Cox, Julie M. Cunningham, Cezary Cybulski, Kamila Czene, Mary B. Daly, Anna DeFazio, Peter Devilee, Orland Dı́ez, Manuela Gago-Domínguez, Jenny Donovan, Thilo Dörk, Eric J. Duell, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Christopher K. Edlund, Digna R. Velez Edwards, Carolina Ellberg, D. Gareth Evans, Peter A. Fasching, Robert L. Ferris, Triantafillos Liloglou, Jane C. Figueiredo, Olivia Fletcher, Renée T. Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven Gallinger, Patricia A. Ganz, Judy E. Garber, José Á. García-Sáenz, Simon A. Gayther, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Ellen L. Goode, Marc T. Goodman, Gary E. Goodman, Kjell Grankvist, Mark H. Greene, Henrik Grönberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C. Hamdy, Robert J. Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun‐Chul Hong, John L. Hopper, Richard S. Houlston, Peter J. Hulick, David J. Hunter, David G. Huntsman, Gregory Idos, Evgeny N. Imyanitov, Sue A. Ingles, Claudine Isaacs, Anna Jakubowska, Paul A. James, Mark A. Jenkins, Mattias Johansson, Mikael Johansson, Esther M. John, Amit D. Joshi, Radka Kaneva, Beth Y. Karlan, Linda E. Kelemen, Tabea Kühl, Kay‐Tee Khaw, Э. К. Хуснутдинова, Adam S. Kibel, Lambertus A. Kiemeney, Jeri Kim, Susanne K. Kjær, Julia A. Knight, Manolis Kogevinas, Zsofia Kote‐Jarai, Stella Koutros, Vessela N. Kristensen, Jolanta Kupryjańczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D. Le, Eunjung Lee, Flavio Lejbkowicz, Heinz‐Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A. Levine, Li Li, Christopher I. Li, Annika Lindblom, Noralane M. Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Mæhle, Christiane Maier, Arto Mannermaa, Loı̈c Le Marchand, Sara Margolin, Taymaa May, Lesley McGuffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L. Milne, Robert J. MacInnis, Francesmary Modugno, Marco Montagna, Vı́ctor Moreno, Kirsten B. Moysich, Lorelei A. Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L. Nathanson, David E. Neal, Andrew R. Ness, Susan L. Neuhausen, Heli Nevanlinna, Polly A. Newcomb, Lisa F. Newcomb, Finn Cilius Nielsen, Liene Ņikitina-Zaķe, Børge G. Nordestgaard, Robert L. Nussbaum, Kenneth Offit, Edith Oláh, Ali Amin Al Olama, Olufunmilayo I. Olopade, Andrew F. Olshan, Håkan Olsson, Ana Osório, Hardev Pandha, Jong Y. Park, Nora Pashayan, Michael T. Parsons, Tanja Pejović, Kathryn L. Penney, Wilbert H.M. Peters, Catherine M. Phelan, Amanda I. Phipps, Dijana Plaseska‐Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kāri Stefánsson, Susan J. Ramus, Leon Raskin, Gad Rennert, Hedy S. Rennert, Elizabeth J. van Rensburg, Marjorie J. Riggan, Harvey A. Risch, Angela Risch, Monique J. Roobol, Barry S. Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Matthew B. Schabath, Johanna Schleutker, Marjanka K. Schmidt, Veronica Wendy Setiawan, Hongbing Shen, Erin M. Siegel, Weiva Sieh, Christian F. Singer, Martha L. Slattery, Karina D. Sørensen, Melissa C. Southey, Amanda B. Spurdle, Janet L. Stanford, Victoria L. Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J. Swerdlow, Eloíza H. Tajara, Catherine M. Tangen, Adonina Tardón, Jack A. Taylor, M. Dawn Teare, Manuel R. Teixeira, Mary Beth Terry, Kathryn L. Terry, Stephen N. Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Paul A. Townsend, Ruth C. Travis, Nadine Tung, Shelley S. Tworoger, Cornelia M. Ulrich, Nawaid Usmani, Celine M. Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel E. Aguado‐Barrera, Qin Wang, Penelope M. Webb, Clarice R. Weinberg, Stephanie J. Weinstein, Mark C. Weissler, Jeffrey N. Weitzel, Catharine West, Emily White, Alice S. Whittemore, H‐Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella J. Woll, Michael O. Woods, Anna H. Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K. Zorn, Jacqueline M. Lane, Richa Saxena, Duncan C. Thomas, Rayjean J. Hung, Brenda Diergaarde, James McKay, Ulrike Peters, Li Hsu, Montserrat García‐Closas, Rosalind A. Eeles, Georgia Chenevix‐Trench, Paul Brennan, Christopher A. Haiman, Jacques Simard, Douglas F. Easton, Stephen B. Gruber, Paul D.P. Pharoah, Alkes L. Price, Bogdan Paşaniuc, Christopher I. Amos, Peter Kraft, Sara Lindström - Nature Communications 2019 被引用: 126

Abstract Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer ( r g = 0.57, p = 4.6 × 10 −8 ), breast and ovarian cancer ( r g = 0.24, p = 7 × 10 −5 ), breast and lung cancer ( r g = 0.18, p =1.5 × 10 −6 ) and breast and colorectal cancer ( r g = 0.15, p = 1.1 × 10 −4 ). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.