Shared heritability and functional enrichment across six solid cancers

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; Bickeböller, 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; Brunnström, Hans; Buchanan, Daniel D; Burwinkel, Barbara; Butzow, Ralf; Cadoni, Gabriella; Caldés, Trinidad; Caligo, Maria A; Campbell, Ian; Campbell, Peter T; Cancel-Tassin, Géraldine; Cannon-Albright, Lisa; Campa, Daniele; Caporaso, Neil; Carvalho, André L; Chan, Andrew T; Chang-Claude, Jenny; Chanock, Stephen J; Chen, Chu; Christiani, David C; Claes, Kathleen B M; Claessens, Frank; Clements, Judith; Collée, 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; Dörk, 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, Renée T; Fostira, Florentia; Franceschi, Silvia; Friedman, Eitan; Gallinger, Steven J; Ganz, Patricia A; Garber, Judy; García-Sáenz, José 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; Guénel, Pascal; Håkansson, Niclas; Hall, Per; Hamann, Ute; Hamdy, Freddie C; Hamilton, Robert J; Hampe, Jochen; Haugen, Aage; Heitz, Florian; Herrero, Rolando; Hillemanns, Peter; Hoffmeister, Michael; Høgdall, 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; Kühl, 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; Lubiński, Jan; Maehle, Lovise; Maier, Christiane; Mannermaa, Arto; Marchand, Loic Le; 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, Børge G; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olama, Ali Amin Al; Olopade, Olufunmilayo I; Olshan, Andrew F; Olsson, Håkan; 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; Tardón, Adonina; Taylor, Jack A; Teare, M Dawn; Teixeira, Manuel R; Terry, Mary Beth; Terry, Kathryn L; Thibodeau, Stephen N; Thomassen, Mads; Bjørge, 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 Elías; 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; García-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; Lindström, Sara

doi:10.1038/s41467-018-08054-4

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Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7477

Title

Shared heritability and functional enrichment across six solid cancers

Author(s)

Date issued

2019-01-25

Citation

Nat Commun. 2019;10(1):431.

Language

Inglés

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 (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 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.

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