Analysis of heritability and shared heritability based on Genome-Wide Association Studies for 13 Cancer Types

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Title: Analysis of heritability and shared heritability based on Genome-Wide Association Studies for 13 Cancer Types
Authors: Sampson, JN
Wheeler, WA
Yeager, M
Panagiotou, O
Wang, Z
Berndt, SI
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, H-O
Ahlbom, A
Albanes, D
Amary, MF
An, S-J
Andersson, U
Andriole, G
Andrulis, IL
Angelucci, E
Ansell, SM
Arici, C
Armstrong, BK
Arslan, AA
Austin, MA
Baris, D
Barkauskas, DA
Bassig, BA
Becker, N
Benavente, Y
Benhamou, S
Berg, C
Van Den Berg, D
Bernstein, L
Bertrand, KA
Birmann, BM
Black, A
Boeing, H
Boffetta, P
Boutron-Ruault, M-C
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, A
Chan, JKC
Chang, ET
Chang, G-C
Chang, I-S
Chang, J
Chang-Claude, J
Chen, C-J
Chen, C-Y
Chen, C
Chen, C-H
Chen, C
Chen, H
Chen, K
Chen, K-Y
Chen, K-C
Chen, Y
Chen, Y-H
Chen, Y-S
Chen, Y-M
Chien, L-H
Chirlaque, M-D
Choi, JE
Choi, YY
Chow, W-H
Chung, CC
Clavel, J
Clavel-Chapelon, F
Cocco, P
Colt, JS
Comperat, E
Conde, L
Connors, JM
Conti, D
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
Fraumeni, JF
Freedman, ND
Freeman, LEB
Fuchs, C
Gago-Dominguez, M
Gallinger, S
Gao, Y-T
Gapstur, SM
Garcia-Closas, M
Garcia-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, M
Hattinger, C
He, Q
He, X
Helzlsouer, K
Henderson, B
Henriksson, R
Hjalgrim, H
Hoffman-Bolton, J
Hohensee, C
Holford, TR
Holly, EA
Hong, Y-C
Hoover, RN
Horn-Ross, PL
Hosain, GMM
Hosgood, HD
Hsiao, C-F
Hu, N
Hu, W
Hu, Z
Huang, M-S
Huerta, J-M
Hung, J-Y
Hutchinson, A
Inskip, PD
Jackson, RD
Jacobs, EJ
Jenab, M
Jeon, H-S
Ji, B-T
Jin, G
Jin, L
Johansen, C
Johnson, A
Jung, YJ
Kaaks, R
Kamineni, A
Kane, E
Kang, CH
Karagas, MR
Kelly, RS
Khaw, K-T
Kim, C
Kim, HN
Kim, JH
Kim, JS
Kim, YH
Kim, YT
Kim, Y-C
Kitahara, CM
Klein, AP
Klein, RJ
Kogevinas, M
Kohno, T
Kolonel, LN
Kooperberg, C
Kricker, A
Krogh, V
Kunitoh, H
Kurtz, RC
Kweon, S-S
LaCroix, A
Lawrence, C
Lecanda, F
Lee, VHF
Li, D
Li, H
Li, J
Li, Y-J
Li, Y
Liao, LM
Liebow, M
Lightfoot, T
Lim, W-Y
Lin, C-C
Lin, D
Lindstrom, S
Linet, MS
Link, BK
Liu, C
Liu, J
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, I-J
Olson, SH
Palli, D
Pao, W
Park, IK
Park, JY
Park, KH
Patino-Garcia, A
Pavanello, S
Peeters, PHM
Perng, R-P
Peters, U
Petersen, GM
Picci, P
Pike, MC
Porru, S
Prescott, J
Prokunina-Olsson, L
Qian, B
Qiao, Y-L
Rais, M
Riboli, E
Riby, J
Risch, HA
Rizzato, C
Rodabough, R
Roman, E
Roupret, M
Ruder, AM
De Sanjose, S
Scelo, G
Schned, A
Schumacher, F
Schwartz, K
Schwenn, M
Scotlandi, K
Seow, A
Serra, C
Serra, M
Sesso, HD
Setiawan, VW
Severi, G
Severson, RK
Shanafelt, TD
Shen, H
Shen, W
Shin, M-H
Shiraishi, K
Shu, X-O
Siddiq, A
Sierrasesumaga, L
Sihoe, ADL
Skibola, CF
Smith, A
Smith, MT
Southey, MC
Spinelli, JJ
Staines, A
Stampfer, M
Stern, MC
Stevens, VL
Stolzenberg-Solomon, RS
Su, J
Su, W-C
Sund, M
Sung, JS
Sung, SW
Tan, W
Tang, W
Tardon, A
Thomas, D
Thompson, CA
Tinker, LF
Tirabosco, R
Tjonneland, A
Travis, RC
Trichopoulos, D
Tsai, F-Y
Tsai, Y-H
Tucker, M
Turner, J
Vajdic, CM
Vermeulen, RCH
Villano, DJ
Vineis, P
Virtamo, J
Visvanathan, K
Wactawski-Wende, J
Wang, C
Wang, C-L
Wang, J-C
Wang, J
Wei, F
Weiderpass, E
Weiner, GJ
Weinstein, S
Wentzensen, N
White, E
Witzig, TE
Wolpin, BM
Wong, MP
Wu, C
Wu, G
Wu, J
Wu, T
Wu, W
Wu, X
Wu, Y-L
Wunder, JS
Xiang, Y-B
Xu, J
Xu, P
Yang, P-C
Yang, T-Y
Ye, Y
Yin, Z
Yokota, J
Yoon, H-I
Yu, C-J
Yu, H
Yu, K
Yuan, J-M
Zelenetz, A
Zeleniuch-Jacquotte, A
Zhang, X-C
Zhang, Y
Zhao, X
Zhao, Z
Zheng, H
Zheng, T
Zheng, W
Zhou, B
Zhu, M
Zucca, M
Boca, SM
Cerhan, JR
Ferri, GM
Hartge, P
Hsiung, CA
Magnani, C
Miligi, L
Morton, LM
Smedby, KE
Teras, LR
Vijai, J
Wang, SS
Brennan, P
Caporaso, NE
Hunter, DJ
Kraft, P
Rothman, N
Silverman, DT
Slager, SL
Chanock, SJ
Chatterjee, N
Item Type: Journal Article
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 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 cases and 34,131 controls. 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, hl2, 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% CI = 14% - 37%) and 7% (4% - 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 non-smoking 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.
Issue Date: 12-Oct-2015
Date of Acceptance: 2-Sep-2015
ISSN: 0027-8874
Publisher: Oxford University Press
Journal / Book Title: JNCI: Journal of the National Cancer Institute
Volume: 107
Issue: 12
Copyright Statement: Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Keywords: Science & Technology
Life Sciences & Biomedicine
Asian Continental Ancestry Group
Bone Neoplasms
European Continental Ancestry Group
Genetic Predisposition to Disease
Genome-Wide Association Study
Kidney Neoplasms
Leukemia, Lymphocytic, Chronic, B-Cell
Lung Neoplasms
Lymphoma, Large B-Cell, Diffuse
Middle Aged
Polymorphism, Single Nucleotide
Testicular Neoplasms
Tissue Array Analysis
Urinary Bladder Neoplasms
Oncology & Carcinogenesis
1112 Oncology And Carcinogenesis
Publication Status: Published
Article Number: ARTN djv279
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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