Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types
Articolo
Data di Pubblicazione:
2015
Abstract:
Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We
aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide
polymorphisms (SNPs) for cancer at 13 anatomical sites.
Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association
studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology
(GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability
attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.
Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl
2,
on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking
characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the
heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of
cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally
statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL)
and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and
bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs
between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that
the genetic etiology for the same disease can vary by population and environmental exposures.
Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for
investigation.
aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide
polymorphisms (SNPs) for cancer at 13 anatomical sites.
Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association
studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology
(GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability
attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.
Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl
2,
on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking
characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the
heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of
cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally
statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL)
and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and
bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs
between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that
the genetic etiology for the same disease can vary by population and environmental exposures.
Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for
investigation.
Tipologia CRIS:
1.1 Articolo in rivista
Elenco autori:
Sampson, Jn; Wheeler, Wa; Yeager, M; Panagiotou, O; Wang, Z; Berndt, S; Lan, Q; Abnet, Cc; Amundadottir, Lt; Figueroa, Jd; Landi, Mt; Mirabello, L; Savage, Sa; Taylor, Pr; De Vivo, I; Mcglynn, Ka; Purdue, Mp; Rajaraman, P; Adami, Ho; Ahlbom, A; Albanes, D; Amary, Mf; An, Sj; Andersson, U; Andriole, G; Andrulis, Il; Angelucci, E; Ansell, Sm; Arici, Cecilia; Armstrong, Bk; Arslan, Aa; Austin, Ma; Baris, D; Barkauskas, Da; Bassig, Ba; Becker, Nir Efraim; Benavente, Y; Benhamou, S; Berg, C; Van Den Berg, D; Bernstein, L; Bertrand, Ka; Birmann, Bm; Black, A; Boeing, H; Boffetta, P; Boutron Ruault, Mc; Bracci, Pm; Brinton, L; Brooks Wilson, Ar; Bueno de Mesquita, Hb; Burdett, L; Buring, J; Butler, Ma; Cai, Q; Cancel Tassin, G; Canzian, F; Carrato, A; Carreon, T; Carta, Angela; Chan, Jk; Chang, Et; Chang, Gc; Chang, Is; Chang, J; Chang Claude, J; Chen, Cj; Chen, Cy; Chen, C; Chen, Ch; Chen, C; Chen, H; Chen, K; Chen, Ky; Chen, Kc; Chen, Y; Chen, Yh; Chen, Ys; Chen, Ym; Chien, Lh; Chirlaque, Md; Choi, Je; Choi, Yy; Chow, Wh; Chung, Cc; Clavel, J; Clavel Chapelon, F; Cocco, P; Colt, Js; Comperat, E; Conde, L; Connors, Jm; Conti, Domenico; Cortessis, Vk; Cotterchio, M; Cozen, W; Crouch, S; Crous Bou, M; Cussenot, O; Davis, Fg; Ding, T; Diver, Wr; Dorronsoro, M; Dossus, L; Duell, Ej; Ennas, Mg; Erickson, Rl; Feychting, M; Flanagan, Am; Foretova, L; Freedman, Nd; Beane Freeman, Le; Fuchs, C; Gago Dominguez, M; Gallinger, S; Gao, Yt; Gapstur, Sm; Garcia Closas, M; García Closas, R; Gascoyne, Rd; Gastier Foster, J; Gaudet, Mm; Gaziano, Jm; Giffen, C; Giles, Gg; Giovannucci, E; Glimelius, B; Goggins, M; Gokgoz, N; Goldstein, Am; Gorlick, R; Gross, M; Grubb, R; Gu, J; Guan, P; Gunter, M; Guo, H; Habermann, Tm; Haiman, Ca; Halai, D; Hallmans, G; Hassan, Mehwish; Hattinger, C; He, Q; He, X; Helzlsouer, K; Henderson, B; Henriksson, R; Hjalgrim, H; Hoffman Bolton, J; Hohensee, C; Holford, Tr; Holly, Ea; Hong, Yc; Hoover, Rn; Horn Ross, Pl; Hosain, Gm; Hosgood, Hd; Hsiao, Cf; Hu, N; Hu, W; Hu, Z; Huang, Ms; Huerta, Jm; Hung, Jy; Hutchinson, A; Inskip, Pd; Jackson, Rd; Jacobs, Ej; Jenab, M; Jeon, Hs; Ji, Bt; Jin, G; Jin, L; Johansen, C; Johnson, Lynnea Ann; Jung, Yj; Kaaks, R; Kamineni, A; Kane, E; Kang, Ch; Karagas, Mr; Kelly, Rs; Khaw, Kt; Kim, C; Kim, Hn; Kim, Jh; Kim, Js; Kim, Yh; Kim, Yt; Kim, Yc; Kitahara, Cm; Klein, Ap; Klein, Rj; Kogevinas, M; Kohno, T; Kolonel, Ln; Kooperberg, C; Kricker, A; Krogh, V; Kunitoh, H; Kurtz, Rc; Kweon, Ss; Lacroix, A; Lawrence, C; Lecanda, F; Lee, Vh; Li, D; Li, H; Li, J; Li, Yj; Li, Y; Liao, Lm; Liebow, M; Lightfoot, T; Lim, Wy; Lin, Cc; Lin, D; Lindstrom, S; Linet, Ms; Link, Bk; Liu, C; Liu, Junxiang; Liu, L; Ljungberg, B; Lloreta, J; Di Lollo, S; Lu, D; Lund, E; Malats, N; Mannisto, S; Le Marchand, L; Marina, N; Masala, G; Mastrangelo, G; Matsuo, K; Maynadie, M; Mckay, J; McKean Cowdin, R; Melbye, M; Melin, Bs; Michaud, Ds; Mitsudomi, T; Monnereau, A; Montalvan, R; Moore, Le; Mortensen, Lm; Nieters, A; North, Ke; Novak, Aj; Oberg, Al; Offit, K; Oh, Ij; Olson, Sh; Palli, D; Pao, W; Park, Ik; Park, Jy; Park, Kh; Patiño Garcia, A; Pavanello, S; Peeters, Ph; Perng, Rp; Peters, U; Petersen, Gm; Picci, P; Pike, Mc; Porru, Stefano; Prescott, J; Prokunina Olsson, L; Qian, B; Qiao, Yl; Rais, M; Riboli, E; Riby, J; Risch, Ha; Rizzato, C; Rodabough, R; Roman, E; Roupret, M; Ruder, Am; Scelo, G; Schned, A; Schumacher, Richard Fabian; Schwartz, K; Schwenn, M; Scotlandi, K; Seow, A; Serra, C; Serra, Mario; Sesso, Hd; Setiawan, Vw; Severi, G; Severson, Rk; Shanafelt, Td; Shen, H; Shen, W; Shin, Mh; Shiraishi, K; Shu, Xo; Siddiq, A; Sierrasesúmaga, L; Sihoe, Ad; Skibola, Cf; Smith, Jenovia Amisti; Smith, Mt; Southey, Mc; Spinelli, Jj; Staines, A; Stampfer, M; Stern, Mc; Stevens, Vl; Stolzenberg Solomon, Rs; Su, J; Su, Wc; Sund, M; Sung, Js; Sung, Sw; Tan, W; Tang, W; Tardón, A; Thomas, D; Thompson, Ca; Tinker, Lf; Tirabosco, R; Tjønneland, A; Travis, Rc; Trichopoulos, D; Tsa
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