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Shared heritability and functional enrichment across six solid cancers.

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.
Authors:
X Jiang, HK Finucane, FR Schumacher, SL Schmit, JP Tyrer, Y Han, K Michailidou, C Lesseur, KB Kuchenbaecker, J Dennis, DV Conti, G Casey, MM Gaudet, JR Huyghe, D Albanes, MC Aldrich, AS Andrew, IL Andrulis, H Anton-Culver, AC Antoniou, NN Antonenkova, SM Arnold, KJ Aronson, BK Arun, EV Bandera, RB Barkardottir, DR Barnes, J Batra, MW Beckmann, J Benitez, S Benlloch, A Berchuck, SI Berndt, H Bickeböller, SA Bien, C Blomqvist, S Boccia, NV Bogdanova, SE Bojesen, MK Bolla, H Brauch, H Brenner, JD Brenton, MN Brook, J Brunet, H Brunnström, DD Buchanan, B Burwinkel, R Butzow, G Cadoni, T Caldés, MA Caligo, I Campbell, PT Campbell, G Cancel-Tassin, L Cannon-Albright, D Campa, N Caporaso, AL Carvalho, AT Chan, J Chang-Claude, SJ Chanock, C Chen, DC Christiani, KBM Claes, F Claessens, J Clements, JM Collée, MC Correa, FJ Couch, A Cox, JM Cunningham, C Cybulski, K Czene, MB Daly, A deFazio, P Devilee, O Diez, M Gago-Dominguez, JL Donovan, T Dörk, EJ Duell, AM Dunning, M Dwek, DM Eccles, CK Edlund, DRV Edwards, C Ellberg, DG Evans, PA Fasching, RL Ferris, T Liloglou, JC Figueiredo, O Fletcher, RT Fortner, F Fostira, S Franceschi, E Friedman, SJ Gallinger, PA Ganz, J Garber, JA García-Sáenz, SA Gayther, GG Giles, AK Godwin, MS Goldberg, DE Goldgar, EL Goode, MT Goodman, G Goodman, K Grankvist, MH Greene, H Gronberg, J Gronwald, P Guénel, N Håkansson, P Hall, U Hamann, FC Hamdy, RJ Hamilton, J Hampe, A Haugen, F Heitz, R Herrero, P Hillemanns, M Hoffmeister, E Høgdall, Y-C Hong, JL Hopper, R Houlston, PJ Hulick, DJ Hunter, DG Huntsman, G Idos, EN Imyanitov, SA Ingles, C Isaacs, A Jakubowska, P James, MA Jenkins, M Johansson, M Johansson, EM John, AD Joshi, R Kaneva, BY Karlan, LE Kelemen, T Kühl, K-T Khaw, E Khusnutdinova, AS Kibel, LA Kiemeney, J Kim, SK Kjaer, JA Knight, M Kogevinas, Z Kote-Jarai, S Koutros, VN Kristensen, J Kupryjanczyk, M Lacko, S Lam, D Lambrechts, MT Landi, P Lazarus, ND Le, E Lee, F Lejbkowicz, H-J Lenz, G Leslie, D Lessel, J Lester, DA Levine, L Li, CI Li, A Lindblom, NM Lindor, G Liu, F Loupakis, J Lubiński, L Maehle, C Maier, A Mannermaa, LL Marchand, S Margolin, T May, L McGuffog, A Meindl, P Middha, A Miller, RL Milne, RJ MacInnis, F Modugno, M Montagna, V Moreno, KB Moysich, L Mucci, K Muir, AM Mulligan, KL Nathanson, DE Neal, AR Ness, SL Neuhausen, H Nevanlinna, PA Newcomb, LF Newcomb, FC Nielsen, L Nikitina-Zake, BG Nordestgaard, RL Nussbaum, K Offit, E Olah, AAA Olama, OI Olopade, AF Olshan, H Olsson, A Osorio, H Pandha, JY Park, N Pashayan, MT Parsons, T Pejovic, KL Penney, WHM Peters, CM Phelan, AI Phipps, D Plaseska-Karanfilska, M Pring, D Prokofyeva, P Radice, K Stefansson, SJ Ramus, L Raskin, G Rennert, HS Rennert, EJ van Rensburg, MJ Riggan, HA Risch, A Risch, MJ Roobol, BS Rosenstein, MA Rossing, K De Ruyck, E Saloustros, DP Sandler, EJ Sawyer, MB Schabath, J Schleutker, MK Schmidt, VW Setiawan, H Shen, EM Siegel, W Sieh, CF Singer, ML Slattery, KD Sorensen, MC Southey, AB Spurdle, JL Stanford, VL Stevens, S Stintzing, J Stone, K Sundfeldt, R Sutphen, AJ Swerdlow, EH Tajara, CM Tangen, A Tardon, JA Taylor, MD Teare, MR Teixeira, MB Terry, KL Terry, SN Thibodeau, M Thomassen, L Bjørge, M Tischkowitz, AE Toland, D Torres, PA Townsend, RC Travis, N Tung, SS Tworoger, CM Ulrich, N Usmani, CM Vachon, E Van Nieuwenhuysen, A Vega, ME Aguado-Barrera, Q Wang, PM Webb, CR Weinberg, S Weinstein, MC Weissler, JN Weitzel, CML West, E White, AS Whittemore, H-E Wichmann, F Wiklund, R Winqvist, A Wolk, P Woll, M Woods, AH Wu, X Wu, D Yannoukakos, W Zheng, S Zienolddiny, A Ziogas, KK Zorn, JM Lane, R Saxena, D Thomas, RJ Hung, B Diergaarde, J McKay, U Peters, L Hsu, M García-Closas, RA Eeles, G Chenevix-Trench, PJ Brennan, CA Haiman, J Simard, DF Easton, SB Gruber, PDP Pharoah, AL Price, B Pasaniuc, CI Amos, P Kraft, S Lindström
Journal:
Nat Commun
Citation info:
10(1):431
Publication date:
25th Jan 2019
Full text
DOI