Publication details

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types

Authors	SAMPSON Joshua N. WHEELER William A. YEAGER Meredith PANAGIOTOU Orestis WANG Zhaoming BERNDT Sonja I. LAN Qing ABNET Christian C. AMUNDADOTTIR Laufey T. FIGUEROA Jonine D. LANDI Maria Teresa MIRABELLO Lisa SAVAGE Sharon A. TAYLOR Philip R. DEVIVO Immaculata MCGLYNN Katherine A. PURDUE Mark P. RAJARAMAN Preetha ADAMI Hans-Olov AHLBOM Anders ALBANES Demetrius AMARY Maria Fernanda AN She-Juan ANDERSSON Ulrika ANDRIOLE Gerald Jr. ANDRULIS Irene L. ANGELUCCI Emanuele ANSELL Stephen M. ARICI Cecilia ARMSTRONG Bruce K. ARSLAN Alan A. AUSTIN Melissa A. BARIS Dalsu BARKAUSKAS Donald A. BASSIG Bryan A. BECKER Nikolaus BENAVENTE Yolanda BENHAMOU Simone BERG Christine VAN DEN BERG David BERNSTEIN Leslie BERTRAND Kimberly A. BIRMANN Brenda M. BLACK Amanda BOEING Heiner BOFFETTA Paolo BOUTRON-RUAULT Marie-Christine BRACCI Paige M. BRINTON Louise BROOKS-WILSON Angela R. BUENO-DE-MESQUITA H. Bas BURDETT Laurie BURING Julie BUTLER Mary Ann CAI Qiuyin CANCEL-TASSIN Geraldine CANZIAN Federico CARRATO Alfredo CARREON Tania CARTA Angela CHAN John K.C. CHANG Ellen T. CHANG Gee-Chen CHANG I-Shou CHANG Jiang CHANG-CLAUDE Jenny CHEN Chien-Jen CHEN Chin-Yi CHEN Chu CHEN Chung-Hsing CHEN Constance CHEN Hongyan CHEN Kexin CHEN Kuan-Yu CHEN Kun-Chieh CHEN Ying CHEN Ying-Hsiang CHEN Yi-Song CHEN Yuh-Min CHIEN Li-Hsin CHIRLAQUE Maria-Dolores CHOI Jin Eun CHOI Yi Young CHOW Wong-Ho CHUNG Charles C. CLAVEL Jacqueline CLAVEL-CHAPELON Franoise COCCO Pierluigi COLT Joanne S. COMPERAT Eva CONDE Lucia CONNORS Joseph M. CONTI David CORTESSIS Victoria K. COTTERCHIO Michelle COZEN Wendy CROUCH Simon CROUS-BOU Marta CUSSENOT Olivier DAVIS Faith G. DING Ti DIVER W. Ryan DORRONSORO Miren DOSSUS Laure DUELL Eric J. ENNAS Maria Grazia ERICKSON Ralph L. FEYCHTING Maria FLANAGAN Adrienne M. FORETOVÁ Lenka FRAUMENI Joseph F. Jr. FREEDMAN Neal D. FREEMAN Laura E. Beane FUCHS Charles GAGO-DOMINGUEZ Manuela GALLINGER Steven GAO Yu-Tang GAPSTUR Susan M. GARCIA-CLOSAS Montserrat GARCIA-CLOSAS Reina GASCOYNE Randy D. GASTIER-FOSTER Julie GAUDET Mia M. GAZIANO J. Michael GIFFEN Carol GILES Graham G. GIOVANNUCCI Edward GLIMELIUS Bengt GOGGINS Michael GOKGOZ Nalan GOLDSTEIN Alisa M. GORLICK Richard GROSS Myron GRUBB Robert III GU Jian GUAN Peng GUNTER Marc GUO Huan HABERMANN Thomas M. HAIMAN Christopher A. HALAI Dina HALLMANS Goran HASSAN Manal HATTINGER Claudia HE Qincheng HE Xingzhou HELZLSOUER Kathy HENDERSON Brian HENRIKSSON Roger HJALGRIM Henrik HOFFMAN-BOLTON Judith HOHENSEE Chancellor HOLFORD Theodore R. HOLLY Elizabeth A. HONG Yun-Chul HOOVER Robert N. HORN-ROSS Pamela L. HOSAIN G.M. Monawar HOSGOOD H. Dean HSIAO Chin-Fu HU Nan HU Wei HU Zhibin HUANG Ming-Shyan HUERTA Jose-Maria HUNG Jen-Yu HUTCHINSON Amy INSKIP Peter D. JACKSON Rebecca D. JACOBS Eric J. JENAB Mazda JEON Hyo-Sung JI Bu-Tian JIN Guangfu JIN Li JOHANSEN Christoffer JOHNSON Alison JUNG Yoo Jin KAAKS Rudolph KAMINENI Aruna KANE Eleanor KANG Cang Hyan KARAGAS Margaret R. KELLY Rachel S. KHAW Kay-Tee KIM Christopher KIM Hee Nam KIM Jin Hee KIM Jun Suk KIM Yeul Hong KIM Young Tae KIM Young Chul KITAHARA Cari M. KLEIN Alison P. KLEIN Robert J. KOGEVINAS Manolis KOHNO Takashi KOLONEL Laurence N. KOOPERBERG Charles KRICKER Anne KROGH Vittorio KUNITOH Hideo KURTZ Robert C. KWEON Sun-Seog LACROIX Andrea LAWRENCE Charles LECANDA Fernando LEE Victor Ho Fun LI Donghui LI Haixin LI Jihua LI Yao-Jen LI Yyqing LIAO Linda M. LIEBOW Mark LIGHTFOOT Tracy LIM Wei-Yen LIN Chien-Chung LIN Dongxin LINDSTROM Sasa LINET Martha S. LINK Brian K. LIU Chenwei LIU Jianjun LIU Li LJUNGBERG Boerje LLORETA Josep DI LOLLO Simonetta LU Daru LUND Eiluv MALATS Nuria MANNISTO Satu LE MARCHAND Loic MARINA Neyssa MASALA Giovanna MASTRANGELO Giuseppe MATSUO Keitaro MAYNADIE Marc MCKAY James MCKEAN-COWDIN Roberta MELBYE Mads MELIN Beatrice S. MICHAUD Dominique S. MITSUDOMI Tetsuya MONNEREAU Alain MONTALVAN Rebecca MOORE Lee E. MORTENSEN Lotte Maxild NIETERS Alexandra NORTH Kari E. NOVAK Anne J. OBERG Ann L. OFFIT Kenneth OH In-Jae OLSON Sara H. PALLI Domenico PAO William PARK In Kyu PARK Jae Yong PARK Kyong Hwa PATINO-GARCIA Ana PAVANELLO Sofia PEETERS Petra H.M. PERNG Reury-Perng PETERS Ulrike PETERSEN Gloria M. PICCI Piero PIKE Malcolm C. PORRU Stefano PRESCOTT Jennifer PROKUNINA-OLSSON Ludmila QIAN Biyun QIAO You-Lin RAIS Marco RIBOLI Elio RIBY Jacques RISCH Harvey A. RIZZATO Cosmeri RODABOUGH Rebecca ROMAN Eve ROUPRET Morgan RUDER Avima M. SANJOSE Silvia de SCELO Ghislaine SCHNED Alan SCHUMACHER Fredrick SCHWARTZ Kendra SCHWENN Molly SCOTLANDI Katia SEOW Adeline SERRA Consol SERRA Massimo SESSO Howard D. SETIAWAN Veronica Wendy SEVERI Gianluca SEVERSON Richard K. SHANAFELT Tait D. SHEN Hongbing SHEN Wei SHIN Min-Ho SHIRAISHI Kouya SHU Xiao-Ou SIDDIQ Afshan SIERRASESUMAGA Luis SIHOE Alan Dart Loon SKIBOLA Christine F. SMITH Alex SMITH Martyn T. SOUTHEY Melissa C. SPINELLI John J. STAINES Anthony STAMPFER Meir STERN Marianna C. STEVENS Victoria L. STOLZENBERG-SOLOMON Rachael S. SU Jian SU Wu-Chou SUND Malin SUNG Jae Sook SUNG Sook Whan TAN Wen TANG Wei TARDON Adonina THOMAS David THOMPSON Carrie A. TINKER Lesley F. TIRABOSCO Roberto TJONNELAND Anne TRAVIS Ruth C. TRICHOPOULOS Dimitrios TSAI Fang-Yu TSAI Ying-Huang TUCKER Margaret TURNER Jenny VAJDIC Claire M. VERMEULEN Roel C. H. VILLANO Danylo J. VINEIS Paolo VIRTAMO Jarmo VISVANATHAN Kala WACTAWSKI-WENDE Jean WANG Chaoyu WANG Chih-Liang WANG Jiu-Cun WANG Junwen WEI Fusheng WEIDERPASS Elisabete WEINER George J. WEINSTEIN Stephanie WENTZENSEN Nicolas WHITE Emily WITZIG Thomas E. WOLPIN Brian M. WONG Maria Pik WU Chen WU Guoping WU Junjie WU Tangchun WU Wei WU Xifeng WU Yi-Long WUNDER Jay S. XIANG Yong-Bing XU Jun XU Ping YANG Pan-Chyr YANG Tsung-Ying YE Yuanqing YIN Zhihua YOKOTA Jun YOON Ho-ll YU Chong-Jen YU Herbert YU Kai YUAN Jian-Min ZELENETZ Andrew ZELENIUCH-JACQUOTTE Anne ZHANG Xu-Chao ZHANG Yawei ZHAO Xueying ZHAO Zhenhong ZHENG Hong ZHENG Tongzhang ZHENG Wei ZHOU Baosen ZHU Meng ZUCCA Mariagrazia BOCA Simina M. CERHAN James R. FERRI Giovanni M. HARTGE Patricia HSIUNG Chao Agnes MAGNANI Corrado MILIGI Lucia MORTON Lindsay M. SMEDBY Karin E. TERAS Lauren R. VIJAI Joseph WANG Sophia S. BRENNAN Paul CAPORASO Neil E. HUNTER David J. KRAFT Peter ROTHMAN Nathaniel SILVERMAN Debra T. SLAGER Susan L. CHANOCK Stephen J. CHATTERJEE Nilanjan
Year of publication	2015
Type	Article in Periodical
Magazine / Source	JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
MU Faculty or unit	Faculty of Medicine
Citation
Doi	http://dx.doi.org/10.1093/jnci/djv279
Field	Oncology and hematology
Keywords	MULTIPLE SUSCEPTIBILITY LOCI; LUNG-CANCER; FAMILIAL RISK; PANCREATIC-CANCER; SWEDEN; INDIVIDUALS; MUTATIONS; RELATIVES; LYMPHOMA; DATABASE
Description	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.