@article{3167965,
    title = "Analysis of Heritability and Shared Heritability Based on Genome-Wide
Association Studies for 13 Cancer Types",
    author = "Sampson, Joshua N. and Wheeler, William A. and Yeager, Meredith and and Panagiotou, Orestis and Wang, Zhaoming and Berndt, Sonja I. and Lan, and Qing and Abnet, Christian C. and Amundadottir, Laufey T. and Figueroa, and Jonine D. and Landi, Maria Teresa and Mirabello, Lisa and Savage, Sharon and A. and Taylor, Philip R. and De Vivo, Immaculata and McGlynn, Katherine and A. and Purdue, Mark P. and Rajaraman, Preetha and Adami, Hans-Olov and and Ahlbom, Anders and Albanes, Demetrius and Amary, Maria Fernanda and An, and She-Juan and Andersson, Ulrika and Andriole, Jr., Gerald and Andrulis, and Irene L. and Angelucci, Emanuele and Ansell, Stephen M. and Arici, and Cecilia and Armstrong, Bruce K. and Arslan, Alan A. and Austin, Melissa and A. and Baris, Dalsu and Barkauskas, Donald A. and Bassig, Bryan A. and and Becker, Nikolaus and Benavente, Yolanda and Benhamou, Simone and Berg, and Christine and Van Den Berg, David and Bernstein, Leslie and Bertrand, and Kimberly A. and Birmann, Brenda M. and Black, Amanda and Boeing, Heiner and and Boffetta, Paolo and Boutron-Ruault, Marie-Christine and Bracci, and Paige M. and Brinton, Louise and Brooks-Wilson, Angela R. and and Bueno-de-Mesquita, H. Bas and Burdett, Laurie and Buring, Julie and and Butler, Mary Ann and Cai, Qiuyin and Cancel-Tassin, Geraldine and and Canzian, Federico and Carrato, Alfredo and Carreon, Tania and Carta, and Angela and Chan, John K. C. and Chang, Ellen T. and Chang, Gee-Chen and and Chang, I-Shou and Chang, Jiang and Chang-Claude, Jenny and Chen, and Chien-Jen and Chen, Chih-Yi and Chen, Chu and Chen, Chung-Hsing and and Chen, Constance and Chen, Hongyan and Chen, Kexin and Chen, Kuan-Yu and and Chen, Kun-Chieh and Chen, Ying and Chen, Ying-Hsiang and Chen, Yi-Song and and Chen, Yuh-Min and Chien, Li-Hsin and Chirlaque, Maria-Dolores and and Choi, Jin Eun and Choi, Yi Young and Chow, Wong-Ho and Chung, Charles C. and and Clavel, Jacqueline and Clavel-Chapelon, Franoise and Cocco, and Pierluigi and Colt, Joanne S. and Comperat, Eva and Conde, Lucia and and Connors, Joseph M. and Conti, David and Cortessis, Victoria K. and and Cotterchio, Michelle and Cozen, Wendy and Crouch, Simon and Crous-Bou, and Marta and Cussenot, Olivier and Davis, Faith G. and Ding, Ti and Diver, and W. Ryan and Dorronsoro, Miren and Dossus, Laure and Duell, Eric J. and and Ennas, Maria Grazia and Erickson, Ralph L. and Feychting, Maria and and Flanagan, Adrienne M. and Foretova, Lenka and Fraumeni, Jr., Joseph F. and and Freedman, Neal D. and Freeman, Laura E. Beane and Fuchs, Charles and and Gago-Dominguez, Manuela and Gallinger, Steven and Gao, Yu-Tang and and Gapstur, Susan M. and Garcia-Closas, Montserrat and Garcia-Closas, Reina and and Gascoyne, Randy D. and Gastier-Foster, Julie and Gaudet, Mia M. and and Gaziano, J. Michael and Giffen, Carol and Giles, Graham G. and and Giovannucci, Edward and Glimelius, Bengt and Goggins, Michael and and Gokgoz, Nalan and Goldstein, Alisa M. and Gorlick, Richard and Gross, and Myron and Grubb, III, Robert and Gu, Jian and Guan, Peng and Gunter, and Marc and Guo, Huan and Habermann, Thomas M. and Haiman, Christopher A. and and Halai, Dina and Hallmans, Goran and Hassan, Manal and Hattinger, and Claudia and He, Qincheng and He, Xingzhou and Helzlsouer, Kathy and and Henderson, Brian and Henriksson, Roger and Hjalgrim, Henrik and and Hoffman-Bolton, Judith and Hohensee, Chancellor and Holford, Theodore R. and and Holly, Elizabeth A. and Hong, Yun-Chul and Hoover, Robert N. and and Horn-Ross, Pamela L. and Hosain, G. M. Monawar and Hosgood, III, H. Dean and and Hsiao, Chin-Fu and Hu, Nan and Hu, Wei and Hu, Zhibin and Huang, and Ming-Shyan and Huerta, Jose-Maria and Hung, Jen-Yu and Hutchinson, Amy and and Inskip, Peter D. and Jackson, Rebecca D. and Jacobs, Eric J. and and Jenab, Mazda and Jeon, Hyo-Sung and Ji, Bu-Tian and Jin, Guangfu and and Jin, Li and Johansen, Christoffer and Johnson, Alison and Jung, Yoo Jin and and Kaaks, Rudolph and Kamineni, Aruna and Kane, Eleanor and Kang, Chang and Hyun and Karagas, Margaret R. and Kelly, Rachel S. and Khaw, Kay-Tee and and Kim, Christopher and Kim, Hee Nam and Kim, Jin Hee and Kim, Jun Suk and and Kim, Yeul Hong and Kim, Young Tae and Kim, Young-Chul and Kitahara, Cari and M. and Klein, Alison P. and Klein, Robert J. and Kogevinas, Manolis and and Kohno, Takashi and Kolonel, Laurence N. and Kooperberg, Charles and and Kricker, Anne and Krogh, Vittorio and Kunitoh, Hideo and Kurtz, Robert and C. and Kweon, Sun-Seog and LaCroix, Andrea and Lawrence, Charles and and Lecanda, Fernando and Lee, Victor Ho Fun and Li, Donghui and Li, Haixin and and Li, Jihua and Li, Yao-Jen and Li, Yuqing and Liao, Linda M. and and Liebow, Mark and Lightfoot, Tracy and Lim, Wei-Yen and Lin, Chien-Chung and and Lin, Dongxin and Lindstrom, Sara and Linet, Martha S. and Link, and Brian K. and Liu, Chenwei and Liu, Jianjun and Liu, Li and Ljungberg, and Boerje and Lloreta, Josep and Di Lollo, Simonetta and Lu, Daru and Lund, and Eiluv and Malats, Nuria and Mannisto, Satu and Le Marchand, Loic and and Marina, Neyssa and Masala, Giovanna and Mastrangelo, Giuseppe and and Matsuo, Keitaro and Maynadie, Marc and Mckay, James and McKean-Cowdin, and Roberta and Melbye, Mads and Melin, Beatrice S. and Michaud, Dominique and S. and Mitsudomi, Tetsuya and Monnereau, Alain and Montalvan, Rebecca and and Moore, Lee E. and Mortensen, Lotte Maxild and Nieters, Alexandra and and North, Kari E. and Novak, Anne J. and Oberg, Ann L. and Offit, Kenneth and and Oh, In-Jae and Olson, Sara H. and Palli, Domenico and Pao, William and and Park, In Kyu and Park, Jae Yong and Park, Kyong Hwa and and Patino-Garcia, Ana and Pavanello, Sofia and Peeters, Petra H. M. and and Perng, Reury-Perng and Peters, Ulrike and Petersen, Gloria M. and Picci, and Piero and Pike, Malcolm C. and Porru, Stefano and Prescott, Jennifer and and Prokunina-Olsson, Ludmila and Qian, Biyun and Qiao, You-Lin and Rais, and Marco and Riboli, Elio and Riby, Jacques and Risch, Harvey A. and and Rizzato, Cosmeri and Rodabough, Rebecca and Roman, Eve and Roupret, and Morgan and Ruder, Avima M. and de Sanjose, Silvia and Scelo, Ghislaine and and Schned, Alan and Schumacher, Fredrick and Schwartz, Kendra and and Schwenn, Molly and Scotlandi, Katia and Seow, Adeline and Serra, Consol and and Serra, Massimo and Sesso, Howard D. and Setiawan, Veronica Wendy and and Severi, Gianluca and Severson, Richard K. and Shanafelt, Tait D. and and Shen, Hongbing and Shen, Wei and Shin, Min-Ho and Shiraishi, Kouya and and Shu, Xiao-Ou and Siddiq, Afshan and Sierrasesumaga, Luis and Sihoe, Alan and Dart Loon and Skibola, Christine F. and Smith, Alex and Smith, Martyn T. and and Southey, Melissa C. and Spinelli, John J. and Staines, Anthony and and Stampfer, Meir and Stern, Marianna C. and Stevens, Victoria L. and and Stolzenberg-Solomon, Rachael S. and Su, Jian and Su, Wu-Chou and Sund, and Malin and Sung, Jae Sook and Sung, Sook Whan and Tan, Wen and Tang, Wei and and Tardon, Adonina and Thomas, David and Thompson, Carrie A. and and Tinker, Lesley F. and Tirabosco, Roberto and Tjonneland, Anne and and Travis, Ruth C. and Trichopoulos, Dimitrios and Tsai, Fang-Yu and Tsai, and Ying-Huang and Tucker, Margaret and Turner, Jenny and Vajdic, Claire M. and and Vermeulen, Roel C. H. and Villano, Danylo J. and Vineis, Paolo and and Virtamo, Jarmo and Visvanathan, Kala and Wactawski-Wende, Jean and Wang, and Chaoyu and Wang, Chih-Liang and Wang, Jiu-Cun and Wang, Junwen and Wei, and Fusheng and Weiderpass, Elisabete and Weiner, George J. and Weinstein, and Stephanie and Wentzensen, Nicolas and White, Emily and Witzig, Thomas E. and and Wolpin, Brian M. and Wong, Maria Pik and Wu, Chen and Wu, Guoping and and Wu, Junjie and Wu, Tangchun and Wu, Wei and Wu, Xifeng and Wu, and Yi-Long and Wunder, Jay S. and Xiang, Yong-Bing and Xu, Jun and Xu, Ping and and Yang, Pan-Chyr and Yang, Tsung-Ying and Ye, Yuanqing and Yin, Zhihua and and Yokota, Jun and Yoon, Ho-Il and Yu, Chong-Jen and Yu, Herbert and and Yu, Kai and Yuan, Jian-Min and Zelenetz, Andrew and Zeleniuch-Jacquotte, and Anne and Zhang, Xu-Chao and Zhang, Yawei and Zhao, Xueying and Zhao, and Zhenhong and Zheng, Hong and Zheng, Tongzhang and Zheng, Wei and Zhou, and Baosen and Zhu, Meng and Zucca, Mariagrazia and Boca, Simina M. and and Cerhan, James R. and Ferri, Giovanni M. and Hartge, Patricia and Hsiung, and Chao Agnes and Magnani, Corrado and Miligi, Lucia and Morton, Lindsay M. and and Smedby, Karin E. and Teras, Lauren R. and Vijai, Joseph and Wang, and Sophia S. and Brennan, Paul and Caporaso, Neil E. and Hunter, David J. and and Kraft, Peter and Rothman, Nathaniel and Silverman, Debra T. and and Slager, Susan L. and Chanock, Stephen J. and Chatterjee, Nilanjan",
    journal = "JNCI Journal of the National Cancer Institute",
    year = "2015",
    volume = "107",
    number = "12",
    publisher = "OXFORD UNIV PRESS INC",
    issn = "0027-8874, 1460-2105",
    doi = "10.1093/jnci/djv279",
    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, h(l)(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
(rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and
pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic
lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung
(rho = 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."
}