Shared heritability and functional enrichment across six solid cancers.

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Journal Article

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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Duke Authors

Cited Authors

  • Jiang, X; Finucane, HK; Schumacher, FR; Schmit, SL; Tyrer, JP; Han, Y; Michailidou, K; Lesseur, C; Kuchenbaecker, KB; Dennis, J; Conti, DV; Casey, G; Gaudet, MM; Huyghe, JR; Albanes, D; Aldrich, MC; Andrew, AS; Andrulis, IL; Anton-Culver, H; Antoniou, AC; Antonenkova, NN; Arnold, SM; Aronson, KJ; Arun, BK; Bandera, EV; Barkardottir, RB; Barnes, DR; Batra, J; Beckmann, MW; Benitez, J; Benlloch, S; Berchuck, A; Berndt, SI; Bickeböller, H; Bien, SA; Blomqvist, C; Boccia, S; Bogdanova, NV; Bojesen, SE; Bolla, MK; Brauch, H; Brenner, H; Brenton, JD; Brook, MN; Brunet, J; Brunnström, H; Buchanan, DD; Burwinkel, B; Butzow, R; Cadoni, G; Caldés, T; Caligo, MA; Campbell, I; Campbell, PT; Cancel-Tassin, G; Cannon-Albright, L; Campa, D; Caporaso, N; Carvalho, AL; Chan, AT; Chang-Claude, J; Chanock, SJ; Chen, C; Christiani, DC; Claes, KBM; Claessens, F; Clements, J; Collée, JM; Correa, MC; Couch, FJ; Cox, A; Cunningham, JM; Cybulski, C; Czene, K; Daly, MB; deFazio, A; Devilee, P; Diez, O; Gago-Dominguez, M; Donovan, JL; Dörk, T; Duell, EJ; Dunning, AM; Dwek, M; Eccles, DM; Edlund, CK; Edwards, DRV; Ellberg, C; Evans, DG; Fasching, PA; Ferris, RL; Liloglou, T; Figueiredo, JC; Fletcher, O; Fortner, RT; Fostira, F; Franceschi, S; Friedman, E; Gallinger, SJ; Ganz, PA; Garber, J; García-Sáenz, JA; Gayther, SA; Giles, GG; Godwin, AK; Goldberg, MS; Goldgar, DE; Goode, EL; Goodman, MT; Goodman, G; Grankvist, K; Greene, MH; Gronberg, H; Gronwald, J; Guénel, P; Håkansson, N; Hall, P; Hamann, U; Hamdy, FC; Hamilton, RJ; Hampe, J; Haugen, A; Heitz, F; Herrero, R; Hillemanns, P; Hoffmeister, M; Høgdall, E; Hong, Y-C; Hopper, JL; Houlston, R; Hulick, PJ; Hunter, DJ; Huntsman, DG; Idos, G; Imyanitov, EN; Ingles, SA; Isaacs, C; Jakubowska, A; James, P; Jenkins, MA; Johansson, M; Johansson, M; John, EM; Joshi, AD; Kaneva, R; Karlan, BY; Kelemen, LE; Kühl, T; Khaw, K-T; Khusnutdinova, E; Kibel, AS; Kiemeney, LA; Kim, J; Kjaer, SK; Knight, JA; Kogevinas, M; Kote-Jarai, Z; Koutros, S; Kristensen, VN; Kupryjanczyk, J; Lacko, M; Lam, S; Lambrechts, D; Landi, MT; Lazarus, P; Le, ND; Lee, E; Lejbkowicz, F; Lenz, H-J; Leslie, G; Lessel, D; Lester, J; Levine, DA; Li, L; Li, CI; Lindblom, A; Lindor, NM; Liu, G; Loupakis, F; LubiƄski, J; Maehle, L; Maier, C; Mannermaa, A; Marchand, LL; Margolin, S; May, T; McGuffog, L; Meindl, A; Middha, P; Miller, A; Milne, RL; MacInnis, RJ; Modugno, F; Montagna, M; Moreno, V; Moysich, KB; Mucci, L; Muir, K; Mulligan, AM; Nathanson, KL; Neal, DE; Ness, AR; Neuhausen, SL; Nevanlinna, H; Newcomb, PA; Newcomb, LF; Nielsen, FC; Nikitina-Zake, L; Nordestgaard, BG; Nussbaum, RL; Offit, K; Olah, E; Olama, AAA; Olopade, OI; Olshan, AF; Olsson, H; Osorio, A; Pandha, H; Park, JY; Pashayan, N; Parsons, MT; Pejovic, T; Penney, KL; Peters, WHM; Phelan, CM; Phipps, AI; Plaseska-Karanfilska, D; Pring, M; Prokofyeva, D; Radice, P; Stefansson, K; Ramus, SJ; Raskin, L; Rennert, G; Rennert, HS; van Rensburg, EJ; Riggan, MJ; Risch, HA; Risch, A; Roobol, MJ; Rosenstein, BS; Rossing, MA; De Ruyck, K; Saloustros, E; Sandler, DP; Sawyer, EJ; Schabath, MB; Schleutker, J; Schmidt, MK; Setiawan, VW; Shen, H; Siegel, EM; Sieh, W; Singer, CF; Slattery, ML; Sorensen, KD; Southey, MC; Spurdle, AB; Stanford, JL; Stevens, VL; Stintzing, S; Stone, J; Sundfeldt, K; Sutphen, R; Swerdlow, AJ; Tajara, EH; Tangen, CM; Tardon, A; Taylor, JA; Teare, MD; Teixeira, MR; Terry, MB; Terry, KL; Thibodeau, SN; Thomassen, M; Bjørge, L; Tischkowitz, M; Toland, AE; Torres, D; Townsend, PA; Travis, RC; Tung, N; Tworoger, SS; Ulrich, CM; Usmani, N; Vachon, CM; Van Nieuwenhuysen, E; Vega, A; Aguado-Barrera, ME; Wang, Q; Webb, PM; Weinberg, CR; Weinstein, S; Weissler, MC; Weitzel, JN; West, CML; White, E; Whittemore, AS; Wichmann, H-E; Wiklund, F; Winqvist, R; Wolk, A; Woll, P; Woods, M; Wu, AH; Wu, X; Yannoukakos, D; Zheng, W; Zienolddiny, S; Ziogas, A; Zorn, KK; Lane, JM; Saxena, R; Thomas, D; Hung, RJ; Diergaarde, B; McKay, J; Peters, U; Hsu, L; García-Closas, M; Eeles, RA; Chenevix-Trench, G; Brennan, PJ; Haiman, CA; Simard, J; Easton, DF; Gruber, SB; Pharoah, PDP; Price, AL; Pasaniuc, B; Amos, CI; Kraft, P; Lindström, S

Published Date

  • January 25, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 431 -

PubMed ID

  • 30683880

Pubmed Central ID

  • 30683880

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-018-08054-4

Language

  • eng

Conference Location

  • England