Shared heritability and functional enrichment across six solid cancers Article

Jiang, X, Finucane, HK, Schumacher, FR et al. (2019). Shared heritability and functional enrichment across six solid cancers . 10(1), 10.1038/s41467-018-08054-4

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

fiu authors

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.

publication date

  • December 1, 2019

Digital Object Identifier (DOI)

volume

  • 10

issue

  • 1