eprintid: 10067104 rev_number: 22 eprint_status: archive userid: 608 dir: disk0/10/06/71/04 datestamp: 2019-02-06 12:50:38 lastmod: 2021-12-02 00:17:38 status_changed: 2019-02-06 12:50:38 type: article metadata_visibility: show creators_name: Jiang, X creators_name: Finucane, HK creators_name: Schumacher, FR creators_name: Schmit, SL creators_name: Tyrer, JP creators_name: Han, Y creators_name: Michailidou, K creators_name: Lesseur, C creators_name: Kuchenbaecker, KB creators_name: Dennis, J creators_name: Conti, DV creators_name: Casey, G creators_name: Gaudet, MM creators_name: Huyghe, JR creators_name: Albanes, D creators_name: Aldrich, MC creators_name: Andrew, AS creators_name: Andrulis, IL creators_name: Anton-Culver, H creators_name: Antoniou, AC creators_name: Antonenkova, NN creators_name: Arnold, SM creators_name: Aronson, KJ creators_name: Arun, BK creators_name: Bandera, EV creators_name: Barkardottir, RB creators_name: Barnes, DR creators_name: Batra, J creators_name: 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creators_name: Amos, CI creators_name: Kraft, P creators_name: Lindström, S title: Shared heritability and functional enrichment across six solid cancers ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D79 divisions: D12 divisions: G21 note: Copyright © The Author(s) 2019 Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. 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. date: 2019-01-25 date_type: published official_url: http://doi.org/10.1038/s41467-018-08054-4 oa_status: green full_text_type: pub pmcid: PMC6347624 language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1624250 doi: 10.1038/s41467-018-08054-4 pii: 10.1038/s41467-018-08054-4 lyricists_name: Kuchenbaecker, Karoline lyricists_name: Pashayan, Nora lyricists_id: KBEKK98 lyricists_id: NPASH45 actors_name: Cuccu, Clara actors_id: CCCUC40 actors_role: owner full_text_status: public publication: Nature Communications volume: 10 number: 1 article_number: 431 event_location: England issn: 2041-1723 citation: Jiang, X; Finucane, HK; Schumacher, FR; Schmit, SL; Tyrer, JP; Han, Y; Michailidou, K; ... Lindström, S; + view all <#> 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; Lubiński, 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; - view fewer <#> (2019) Shared heritability and functional enrichment across six solid cancers. Nature Communications , 10 (1) , Article 431. 10.1038/s41467-018-08054-4 <https://doi.org/10.1038/s41467-018-08054-4>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10067104/1/Jiang_s41467-018-08054-4.pdf