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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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.; Aronsen, 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.; Bickeboller, 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, Geraldine; 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.; Grönberg, 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.; Kuhl, Tabea; Khaw, Kay-Tee; Khusnutdinova, Elza; Kibel, Adam S.; Kiemeney, Lambertus A.; Kim, Jeri; Kjær, 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; Mæhle, Lovise Olaug; 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, Marthaa L.; Sørensen, 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; 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 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; 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