Shared heritability and functional enrichment across six solid cancers.
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Date
2019-01-25ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Subject
Humans
Breast Neoplasms
Colorectal Neoplasms
Ovarian Neoplasms
Head and Neck Neoplasms
Lung Neoplasms
Prostatic Neoplasms
Genetic Predisposition to Disease
Neoplasm Proteins
Case-Control Studies
Smoking
Mental Disorders
Inheritance Patterns
Phenotype
Polymorphism, Single Nucleotide
European Continental Ancestry Group
Female
Male
Genome-Wide Association Study
Research team
Functional Genetic Epidemiology
Aetiological Epidemiology
Cancer Genomics
Oncogenetics
Language
eng
Date accepted
2018-12-10
License start date
2019-01-25
Citation
Nature communications, 2019, 10 (1), pp. 431 - ?
Publisher
NATURE PORTFOLIO
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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