Shared heritability and functional enrichment across six solid cancers

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

作者机构：Harvard TH Chan Sch Publ Hlth Program Genet Epidemiol & Stat Genet 677 Huntington Ave Boston MA 02115 USA Karolinska Inst Inst Environm Med Unit Cardiovasc Epidemiol Nobels Vagen 13 S-17177 Stockholm Sweden Harvard TH Chan Sch Publ Hlth Dept Epidemiol 677 Huntington Ave Boston MA 02115 USA Broad Inst MIT & Harvard Program Med & Populat Genet 75 Ames St Cambridge MA 02142 USA Case Western Reserve Univ Dept Populat & Quantitat Hlth Sci 10900 Eucid Ave Cleveland OH 44106 USA Univ Hosp Seidman Canc Ctr Cleveland OH 44106 USA H Lee Moffitt Canc Ctr & Res Inst Dept Canc Epidemiol 12902 Magnolia Dr MRC CANCONT Tampa FL 33612 USA H Lee Moffitt Canc Ctr & Res Inst Dept Gastrointestinal Oncol 12902 Magnolia Dr MRC CANCONT Tampa FL 33612 USA Univ Cambridge Dept Oncol Ctr Canc Genet Epidemiol 2 Worts Causeway Cambridge CB1 8RN England Geisel Sch Med Dartmouth Dept Biomed Data Sci 1 Med Ctr Dr Dartmouth NS Lebanon Univ Cambridge Dept Publ Hlth & Primary Care Ctr Canc Genet Epidemiol 2 Worts Causeway Cambridge CB1 8RN England Cyprus Inst Neurol & Genet Dept Elect Microscopy Mol Pathol CY-1683 Nicosia Cyprus Int Agcy Res Canc Genet Epidemiol Grp 150 Cours Albert Thomas F-69008 Lyon France Int Agcy Res Canc Sect Genet 150 Cours Albert Thomas F-69008 Lyon France UCL Div Psychiat Maple House149 Tottenham Court Rd London W1T 7NF England UCL UCL Genet Inst Gower St London WC1E 6BT England Univ Southern Calif Keck Sch Med Dept Prevent Med Norris Comprehens Canc Ctr Los Angeles CA 48109 USA Univ Virginia Publ Hlth Sci POB 800717 Charlottesville VI 80071 USA Univ Virginia Ctr Publ Hlth Genom POB 800717 Charlottesville VI 80071 USA Amer Canc Soc Epidemiol Res Program 250 Williams St NW Atlanta GA 30303 USA Fred Hutchinson Canc Res Ctr Div Publ Hlth Sci 1100 Fairview Ave N Seattle WA 98109 USA NCI Div Canc Epidemiol & Genet 9609 Med Ctr Dr Rockville MD 20850 USA Vanderbilt Univ Div Epidemiol Dept Thorac Surg Med Ctr 609 Oxford House Nashville TN 37232 USA Dartmouth Hitchcock Med Ctr 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出 版 物：《NATURE COMMUNICATIONS》 (自然通信)

年 卷 期：2019年第10卷第1期

页      面：431页

核心收录：

学科分类：07[理学] 08[工学] 

基　　金：MRC [MC_PC_14105, MR/N003284/1] Funding Source: UKRI National Cancer Institute [ZIACP010145, K24CA169004] Funding Source: NIH RePORTER 

摘      要：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 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 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.