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.
| Original language | English |
|---|---|
| Article number | djv279 |
| Number of pages | 11 |
| Journal | Journal of the National Cancer Institute |
| Volume | 107 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2015 |
| Externally published | Yes |
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
-
SDG 3 Good Health and Well-being
Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: Journal of the National Cancer Institute, Vol. 107, No. 12, djv279, 12.2015.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Analysis of heritability and shared heritability based on genome-wide association studies for thirteen cancer types
AU - Sampson, Joshua N.
AU - Wheeler, William A.
AU - Yeager, Meredith
AU - Panagiotou, Orestis
AU - Wang, Zhaoming
AU - Berndt, Sonja I.
AU - Lan, Qing
AU - Abnet, Christian C.
AU - Amundadottir, Laufey T.
AU - Figueroa, Jonine D
AU - Landi, Maria Teresa
AU - Mirabello, Lisa
AU - Savage, Sharon A.
AU - Taylor, Philip R.
AU - De Vivo, Immaculata
AU - McGlynn, Katherine A.
AU - Purdue, Mark P.
AU - Rajaraman, Preetha
AU - Adami, Hans Olov
AU - Ahlbom, Anders
AU - Albanes, Demetrius
AU - Amary, Maria Fernanda
AU - An, She Juan
AU - Andersson, Ulrika
AU - Andriole, Gerald L
AU - Andrulis, Irene L
AU - Angelucci, Emanuele
AU - Ansell, Stephen M.
AU - Arici, Cecilia
AU - Armstrong, Bruce K
AU - Arslan, Alan A.
AU - Austin, Melissa A.
AU - Baris, Dalsu
AU - Barkauskas, Donald A.
AU - Bassig, Bryan A.
AU - Becker, Nikolaus
AU - Benavente, Yolanda
AU - Benhamou, Simone
AU - Berg, Christine D
AU - Berg, David
AU - Bernstein, Leslie
AU - Bertrand, Kimberly A.
AU - Birmann, Brenda M.
AU - Black, Amanda
AU - Boeing, Heiner
AU - Boffetta, Paolo
AU - Boutron-Ruault, Marie Christine
AU - Bracci, Paige M.
AU - Brinton, Louise
AU - Brooks-Wilson, Angela R.
AU - Bueno de Mesquita, H Bas
AU - Burdett, Laurie
AU - Buring, Julie E
AU - Butler, Mary Ann
AU - Cai, Qiuyin
AU - Cancel-Tassin, Geraldine
AU - Canzian, Federico
AU - Carrato, Alfredo
AU - Carreon, Tania
AU - Carta, Angela
AU - Chan, John K.C.
AU - Chang, Ellen T.
AU - Chang, Gee Chen
AU - Chang, I. Shou
AU - Chang, Jiang
AU - Chang-Claude, Jenny
AU - Chen, Chien-Jen
AU - Chen, Chih Yi
AU - Chen, Chu-Chih
AU - Chen, Chung Hsing
AU - Chen, Constance
AU - Chen, Hongyan
AU - Chen, Kexin
AU - Chen, Kuan Yu
AU - Chen, Kun Chieh
AU - Chen, Ying
AU - Chen, Yi Song
AU - Chen, Yuh Min
AU - Chien, Li Hsin
AU - Chirlaque, María Dolores
AU - Choi, Jin Eun
AU - Choi, Young-Il
AU - Chow, Wong-Ho
AU - Chung, Charles C.
AU - Clavel, Jacqueline
AU - Clavel-Chapelon, Françoise
AU - Cocco, Pierluigi
AU - Colt, Joanne S.
AU - Comperat, Eva
AU - Conde, Lucia
AU - Connors, Joseph M
AU - Conti, David V
AU - Cortessis, Victoria K.
AU - Cotterchio, Michelle
AU - Cozen, Wendy
AU - Crouch, Simon
AU - Crous Bou, Marta
AU - Cussenot, Olivier
AU - Davis, Faith G.
AU - Ding, Ti
AU - Diver, William Ryan
AU - Dorronsoro, Miren
AU - Dossus, Laure
AU - Duell, Eric J.
AU - Ennas, Maria Grazia
AU - Erickson, Ralph L.
AU - Feychting, Maria
AU - Flanagan, Adrienne M.
AU - Foretova, Lenka
AU - Fraumeni, Joseph F.
AU - Freedman, Neal D.
AU - Freeman, Laura E.Beane
AU - Fuchs, Charles S
AU - Gago-Dominguez, Manuela
AU - Gallinger, Steven
AU - Gao, Yu-Tang
AU - Gapstur, Susan M.
AU - Garcia-Closas, Montserrat
AU - García-Closas, Reina
AU - Gascoyne, Randy D
AU - Gastier-Foster, Julie M
AU - Gaudet, Mia M
AU - Gaziano, J. Michael
AU - Giffen, Carol
AU - Giles, Graham G.
AU - Giovannucci, Edward
AU - Glimelius, Bengt
AU - Goggins, Michael
AU - Gokgoz, Nalan
AU - Goldstein, Alisa M
AU - Gorlick, Richard
AU - Gross, Myron
AU - Grubb, Robert
AU - Gu, Jian Qiang
AU - Guan, Ong Peng
AU - Gunter, Marc
AU - Guo, Huan
AU - Habermann, Thomas M.
AU - Haiman, Christopher A
AU - Halai, Dina
AU - Hallmans, Goran
AU - Hassan, Manal
AU - Hattinger, Claudia
AU - He, Qincheng
AU - He, Xingzhou
AU - Helzlsouer, Kathy J.
AU - Henderson, Brian E
AU - Henriksson, Roger
AU - Hjalgrim, Henrik
AU - Hoffman-Bolton, Judith
AU - Hohensee, Chancellor
AU - Holford, Theodore R.
AU - Holly, Elizabeth A.
AU - Hong, Yun Chul
AU - Hoover, Robert N
AU - Horn-Ross, Pamela L.
AU - Hosain, G. M.Monawar
AU - Hosgood, H. Dean
AU - Hsiao, Chin Fu
AU - Hu, Nan
AU - Hu, Wei
AU - Hu, Zhibin
AU - Huang, Ming Shyan
AU - Huerta, Jose Maria
AU - Hung, Jen Yu
AU - Hutchinson, Amy
AU - Inskip, Peter D.
AU - Jackson, Rebecca D.
AU - Jacobs, Eric J.
AU - Jenab, Mazda
AU - Jeon, Hyo Sung
AU - Ji, Bu-tian
AU - Jin, Guangfu
AU - Jin, Li
AU - Johansen, Christoffer
AU - Johnson, Alison
AU - Jung, Yoo Jin
AU - Kaaks, Rudolph
AU - Kamineni, Aruna
AU - Kane, Eleanor
AU - Kang, Chang Hyun
AU - Karagas, Margaret R.
AU - Kelly, Rachel S.
AU - Khaw, Kay-Tee
AU - Kim, Christopher
AU - Kim, Hee Nam
AU - Kim, Hee-Jin
AU - Kim, Jun Suk
AU - Kim, Yeul Hong
AU - Kim, Young Tae
AU - Kitahara, Cari M.
AU - Klein, Alison P
AU - Klein, Robert J.
AU - Kogevinas, Manolis
AU - Kohno, Takashi
AU - Kolonel, Laurence N
AU - Kooperberg, Charles
AU - Kricker, Anne
AU - Krogh, Vittorio
AU - Kunitoh, Hideo
AU - Kurtz, Robert C.
AU - Kweon, Sun Seog
AU - La Croix, Andrea
AU - Lawrence, Charles
AU - Lecanda, Fernando
AU - Lee, Victor Ho Fun
AU - Li, Donghui
AU - Li, Haixin
AU - Li, Jihua
AU - Li, Yao Jen
AU - Li, Yuqing
AU - Liao, Linda M.
AU - Liebow, Mark
AU - Lightfoot, Tracy
AU - Lim, Wei Yen
AU - Lin, Chien Chung
AU - Lin, Dongxin
AU - Lindstrom, Sara
AU - Linet, Martha S.
AU - Link, Brian K.
AU - Liu, Chenwei
AU - Liu, Jianjun
AU - Liu, Li
AU - Ljungberg, Börje
AU - Lloreta, Josep
AU - Di Lollo, Simonetta
AU - Lu, Daru
AU - Lund, Eiluv
AU - Malats, Nuria
AU - Mannisto, Satu
AU - Marchand, Loic Le
AU - Marina, Neyssa
AU - Masala, Giovanna
AU - Mastrangelo, Giuseppe
AU - Matsuo, Keitaro
AU - Maynadie, Marc
AU - McKay, James
AU - McKean-Cowdin, Roberta
AU - Melbye, Mads
AU - Melin, Beatrice S.
AU - Michaud, Dominique S.
AU - Mitsudomi, Tetsuya
AU - Monnereau, Alain
AU - Montalvan, Rebecca
AU - Moore, Lee E.
AU - Mortensen, Lotte Maxild
AU - Nieters, Alexandra
AU - North, Kari E.
AU - Novak, Anne J.
AU - Oberg, Ann L.
AU - Offit, Kenneth
AU - Oh, In Jae
AU - Olson, Sara H
AU - Palli, Domenico
AU - Pao, William
AU - Park, In Kyu
AU - Park, Jae Yong
AU - Park, Kyong Hwa
AU - Patiño-Garcia, Ana
AU - Pavanello, Sofia
AU - Peeters, Petra H.M.
AU - Perng, Reury Perng
AU - Peters, Ulrike
AU - Petersen, Gloria M
AU - Picci, Piero
AU - Pike, Malcolm C
AU - Porru, Stefano
AU - Prescott, Jennifer
AU - Prokunina-Olsson, Ludmila
AU - Qian, Biyun
AU - Qiao, You Lin
AU - Rais, Marco
AU - Riboli, Elio B
AU - Riby, Jacques
AU - Risch, Harvey A
AU - Rizzato, Cosmeri
AU - Rodabough, Rebecca
AU - Roman, Eve
AU - Roupret, Morgan
AU - Ruder, Avima M.
AU - de Sanjose, Silvia
AU - Scelo, Ghislaine
AU - Schned, Alan
AU - Schumacher, Fredrick
AU - Schwartz, Kendra L.
AU - Schwenn, Molly
AU - Scotlandi, Katia
AU - Seow, Adeline
AU - Serra, Consol
AU - Serra, Massimo
AU - Sesso, Howard D.
AU - Setiawan, Veronica Wendy
AU - Severi, Gianluca
AU - Severson, Richard K.
AU - Shanafelt, Tait D.
AU - Shen, Hongbing
AU - Shen, Wei
AU - Shin, Min Ho
AU - Shiraishi, Kouya
AU - Shu, Xiao-Ou
AU - Siddiq, Afshan
AU - Sierrasesúmaga, Luis
AU - Sihoe, Alan Dart Loon
AU - Skibola, Christine F.
AU - Smith, Alex
AU - Smith, Martyn T.
AU - Southey, Melissa C.
AU - Spinelli, John J.
AU - Staines, Anthony
AU - Stampfer, Meir Jonathan
AU - Stern, Marianna C.
AU - Stevens, Victoria L.
AU - Stolzenberg-Solomon, Rachael
AU - Su, Jian
AU - Su, Wu Chou
AU - Sund, Malin
AU - Sung, Jae Sook
AU - Sung, Sook Whan
AU - Tan, Wen
AU - Tang, Wei
AU - Tardón, Adonina
AU - Thomas, David
AU - Thompson, Carrie A.
AU - Tinker, Lesley F.
AU - Tirabosco, Roberto
AU - Tjønneland, Anne
AU - Travis, Ruth C
AU - Trichopoulos, Dimitrios
AU - Tsai, Fang Yu
AU - Tsai, Ying Huang
AU - Tucker, Margaret
AU - Turner, Jenny
AU - Vajdic, Claire M
AU - Vermeulen, Roel C.H.
AU - Villano, Danylo J.
AU - Vineis, Paolo
AU - Virtamo, Jarmo
AU - Visvanathan, Kala
AU - Wactawski-Wende, Jean
AU - Wang, Chaoyu
AU - Wang, Chih Liang
AU - Wang, Jiu Cun
AU - Wang, Junwen
AU - Wei, Fusheng
AU - Weiderpass, Elisabete
AU - Weiner, George J.
AU - Weinstein, Stephanie
AU - Wentzensen, Nicolas
AU - White, Emily
AU - Witzig, Thomas E.
AU - Wolpin, Brian M.
AU - Wong, Maria Pik
AU - Wu, Chen
AU - Wu, Guoping
AU - Wu, Junjie
AU - Wu, Tangchun
AU - Wu, Wei
AU - Wu, Xifeng
AU - Wu, Yi Long
AU - Wunder, Jay S.
AU - Xiang, Yong-Bing
AU - Xu, Jun
AU - Xu, Ping
AU - Yang, Pan Chyr
AU - Yang, Tsung Ying
AU - Ye, Yuanqing
AU - Yin, Zhihua
AU - Yokota, Jun
AU - Yoon, Ho Il
AU - Yu, Chong Jen
AU - Yu, Herbert
AU - Yu, Kai
AU - Yuan, Jian Min
AU - Zelenetz, Andrew
AU - Zeleniuch-Jacquotte, Anne
AU - Zhang, Xu Chao
AU - Zhang, Yawei
AU - Zhao, Xueying
AU - Zhao, Zhenhong
AU - Zheng, Hong
AU - Zheng, Tongzhang
AU - Zheng, Wei
AU - Zhou, Baosen
AU - Zhu, Meng
AU - Zucca, Mariagrazia
AU - Boca, Simina M.
AU - Cerhan, James R.
AU - Ferri, Giovanni M.
AU - Hartge, Patricia
AU - Hsiung, Chao Agnes
AU - Magnani, Corrado
AU - Miligi, Lucia
AU - Morton, Lindsay M.
AU - Smedby, Karin E.
AU - Teras, Lauren R.
AU - Vijai, Joseph
AU - Wang, Sophia S.
AU - Brennan, Paul
AU - Caporaso, Neil E.
AU - Hunter, David J.
AU - Kraft, Peter
AU - Rothman, Nathaniel
AU - Silverman, Debra T.
AU - Slager, Susan L.
AU - Chanock, Stephen J
AU - Chatterjee, Nilanjan
PY - 2015/12
Y1 - 2015/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84981719326
U2 - 10.1093/jnci/djv279
DO - 10.1093/jnci/djv279
M3 - Article
C2 - 26464424
AN - SCOPUS:84981719326
SN - 0027-8874
VL - 107
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 12
M1 - djv279
ER -