Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
Forouzanfar, Mohammad H; Alexander, Lily; Anderson, H Ross; Bachman, Victoria F; Biryukov, Stan; Brauer, Michael; Burnett, Richard; Casey, Daniel; Coates, Matthew M; Cohen, Aaron; Delwiche, Kristen; Estep, Kara; Frostad, Joseph J; Astha, K C; Kyu, Hmwe H; Moradi-Lakeh, Maziar; Ng, Marie; Slepak, Erica Leigh; Thomas, Bernadette A; Wagner, Joseph; Aasvang, Gunn Marit; Abbafati, Cristiana; Abbasoglu Ozgoren, Ayse; Abd-Allah, Foad; Abera, Semaw F; Aboyans, Victor; Abraham, Biju; Abraham, Jerry Puthenpurakal; Abubakar, Ibrahim; Abu-Rmeileh, Niveen M E; Aburto, Tania C; Achoki, Tom; Adelekan, Ademola; Adofo, Koranteng; Adou, Arsene K; Adsuar, Jose C; Afshin, Ashkan; Agardh, Emilie E; Al Khabouri, Mazin J; Al Lami, Faris H; Alam, Sayed Saidul; Alasfoor, Deena; Albittar, Mohammed I; Alegretti, Miguel A; Aleman, Alicia V; Alemu, Zewdie A; Alfonso-Cristancho, Rafael; Alhabib, Samia; Ali, Raghib; Ali, Mohammed K; Alla, Francois; Allebeck, Peter; Allen, Peter J; Alsharif, Ubai; Alvarez, Elena; Alvis-Guzman, Nelson; Amankwaa, Adansi A; Amare, Azmeraw T; Ameh, Emmanuel A; Ameli, Omid; Amini, Heresh; Ammar, Walid; Anderson, Benjamin O; Antonio, Carl Abelardo T; Anwari, Palwasha; Argeseanu Cunningham, Solveig; Arnlov, Johan; Arsenijevic, Valentina S Arsic; Artaman, Al; Asghar, Rana J; Assadi, Reza; Atkins, Lydia S; Atkinson, Charles; Avila, Marco A; Awuah, Baffour; Badawi, Alaa; Bahit, Maria C; Bakfalouni, Talal; Balakrishnan, Kalpana; Balalla, Shivanthi; Balu, Ravi Kumar; Banerjee, Amitava; Barber, Ryan M; Barker-Collo, Suzanne L; Barquera, Simon; Barregard, Lars; Barrero, Lope H; Barrientos-Gutierrez, Tonatiuh; Basto-Abreu, Ana C; Basu, Arindam; Basu, Sanjay; Basulaiman, Mohammed O; Batis Ruvalcaba, Carolina; Beardsley, Justin; Bedi, Neeraj; Bekele, Tolesa; Bell, Michelle L; Benjet, Corina; Bennett, Derrick A; Benzian, Habib; Bernabe, Eduardo; Beyene, Tariku J; Bhala, Neeraj; Bhalla, Ashish; Bhutta, Zulfiqar A; Bikbov, Boris; Bin Abdulhak, Aref A; Blore, Jed D; Blyth, Fiona M; Bohensky, Megan A; Bora Basara, Berrak; Borges, Guilherme; Bornstein, Natan M; Bose, Dipan; Boufous, Soufiane; Bourne, Rupert R; Brainin, Michael; Brazinova, Alexandra; Breitborde, Nicholas J; Brenner, Hermann; Briggs, Adam D M; Broday, David M; Brooks, Peter M; Bruce, Nigel G; Brugha, Traolach S; Brunekreef, Bert; Buchbinder, Rachelle; Bui, Linh N; Bukhman, Gene; Bulloch, Andrew G; Burch, Michael; Burney, Peter G J; Campos-Nonato, Ismael R; Campuzano, Julio C; Cantoral, Alejandra J; Caravanos, Jack; Cardenas, Rosario; Cardis, Elisabeth; Carpenter, David O; Caso, Valeria; Castaneda-Orjuela, Carlos A; Castro, Ruben E; Catala-Lopez, Ferran; Cavalleri, Fiorella; Cavlin, Alanur; Chadha, Vineet K; Chang, Jung-Chen; Charlson, Fiona J; Chen, Honglei; Chen, Wanqing; Chen, Zhengming; Chiang, Peggy P; Chimed-Ochir, Odgerel; Chowdhury, Rajiv; Christophi, Costas A; Chuang, Ting-Wu; Chugh, Sumeet S; Cirillo, Massimo; Classen, Thomas K D; Colistro, Valentina; Colomar, Mercedes; Colquhoun, Samantha M; Contreras, Alejandra G; Cooper, Cyrus; Cooperrider, Kimberly; Cooper, Leslie T; Coresh, Josef; Courville, Karen J; Criqui, Michael H; Cuevas-Nasu, Lucia; Damsere-Derry, James; Danawi, Hadi; Dandona, Lalit; Dandona, Rakhi; Dargan, Paul I; Davis, Adrian; Davitoiu, Dragos V; Dayama, Anand; de Castro, E Filipa; De la Cruz-Gongora, Vanessa; De Leo, Diego; de Lima, Graca; Degenhardt, Louisa; del Pozo-Cruz, Borja; Dellavalle, Robert P; Deribe, Kebede; Derrett, Sarah; Des Jarlais, Don C; Dessalegn, Muluken; deVeber, Gabrielle A; Devries, Karen M; Dharmaratne, Samath D; Dherani, Mukesh K; Dicker, Daniel; Ding, Eric L; Dokova, Klara; Dorsey, E Ray; Driscoll, Tim R; Duan, Leilei; Durrani, Adnan M; Ebel, Beth E; Ellenbogen, Richard G; Elshrek, Yousef M; Endres, Matthias; Ermakov, Sergey P; Erskine, Holly E; Eshrati, Babak; Esteghamati, Alireza; Fahimi, Saman; Faraon, Emerito Jose A; Farzadfar, Farshad; Fay, Derek F J; Feigin, Valery L; Feigl, Andrea B; Fereshtehnejad, Seyed-Mohammad; Ferrari, Alize J; Ferri, Cleusa P; Flaxman, Abraham D; Fleming, Thomas D; Foigt, Nataliya; Foreman, Kyle J; Paleo, Urbano Fra; Franklin, Richard C; Gabbe, Belinda; Gaffikin, Lynne; Gakidou, Emmanuela; Gamkrelidze, Amiran; Gankpe, Fortune G; Gansevoort, Ron T; Garcia-Guerra, Francisco A; Gasana, Evariste; Geleijnse, Johanna M; Gessner, Bradford D; Gething, Pete; Gibney, Katherine B; Gillum, Richard F; Ginawi, Ibrahim A M; Giroud, Maurice; Giussani, Giorgia; Goenka, Shifalika; Goginashvili, Ketevan; Gomez Dantes, Hector; Gona, Philimon; Gonzalez de Cosio, Teresita; Gonzalez-Castell, Dinorah; Gotay, Carolyn C; Goto, Atsushi; Gouda, Hebe N; Guerrant, Richard L; Gugnani, Harish C; Guillemin, Francis; Gunnell, David; Gupta, Rahul; Gupta, Rajeev; Gutierrez, Reyna A; Hafezi-Nejad, Nima; Hagan, Holly; Hagstromer, Maria; Halasa, Yara A; Hamadeh, Randah R; Hammami, Mouhanad; Hankey, Graeme J; Hao, Yuantao; Harb, Hilda L; Haregu, Tilahun Nigatu; Haro, Josep Maria; Havmoeller, Rasmus; Hay, Simon I; Hedayati, Mohammad T; Heredia-Pi, Ileana B; Hernandez, Lucia; Heuton, Kyle R; Heydarpour, Pouria; Hijar, Martha; Hoek, Hans W; Hoffman, Howard J; Hornberger, John C; Hosgood, H Dean; Hoy, Damian G; Hsairi, Mohamed; Hu, Guoqing; Hu, Howard; Huang, Cheng; Huang, John J; Hubbell, Bryan J; Huiart, Laetitia; Husseini, Abdullatif; Iannarone, Marissa L; Iburg, Kim M; Idrisov, Bulat T; Ikeda, Nayu; Innos, Kaire; Inoue, Manami; Islami, Farhad; Ismayilova, Samaya; Jacobsen, Kathryn H; Jansen, Henrica A; Jarvis, Deborah L; Jassal, Simerjot K; Jauregui, Alejandra; Jayaraman, Sudha; Jeemon, Panniyammakal; Jensen, Paul N; Jha, Vivekanand; Jiang, Fan; Jiang, Guohong; Jiang, Ying; Jonas, Jost B; Juel, Knud; Kan, Haidong; Kany Roseline, Sidibe S; Karam, Nadim E; Karch, Andre; Karema, Corine K; Karthikeyan, Ganesan; Kaul, Anil; Kawakami, Norito; Kazi, Dhruv S; Kemp, Andrew H; Kengne, Andre P; Keren, Andre; Khader, Yousef S; Khalifa, Shams Eldin Ali Hassan; Khan, Ejaz A; Khang, Young-Ho; Khatibzadeh, Shahab; Khonelidze, Irma; Kieling, Christian; Kim, Daniel; Kim, Sungroul; Kim, Yunjin; Kimokoti, Ruth W; Kinfu, Yohannes; Kinge, Jonas M; Kissela, Brett M; Kivipelto, Miia; Knibbs, Luke D; Knudsen, Ann Kristin; Kokubo, Yoshihiro; Kose, M Rifat; Kosen, Soewarta; Kraemer, Alexander; Kravchenko, Michael; Krishnaswami, Sanjay; Kromhout, Hans; Ku, Tiffany; Kuate Defo, Barthelemy; Kucuk Bicer, Burcu; Kuipers, Ernst J; Kulkarni, Chanda; Kulkarni, Veena S; Kumar, G Anil; Kwan, Gene F; Lai, Taavi; Lakshmana Balaji, Arjun; Lalloo, Ratilal; Lallukka, Tea; Lam, Hilton; Lan, Qing; Lansingh, Van C; Larson, Heidi J; Larsson, Anders; Laryea, Dennis O; Lavados, Pablo M; Lawrynowicz, Alicia E; Leasher, Janet L; Lee, Jong-Tae; Leigh, James; Leung, Ricky; Levi, Miriam; Li, Yichong; Li, Yongmei; Liang, Juan; Liang, Xiaofeng; Lim, Stephen S; Lindsay, M Patrice; Lipshultz, Steven E; Liu, Shiwei; Liu, Yang; Lloyd, Belinda K; Logroscino, Giancarlo; London, Stephanie J; Lopez, Nancy; Lortet-Tieulent, Joannie; Lotufo, Paulo A; Lozano, Rafael; Lunevicius, Raimundas; Ma, Jixiang; Ma, Stefan; Machado, Vasco M P; MacIntyre, Michael F; Magis-Rodriguez, Carlos; Mahdi, Abbas A; Majdan, Marek; Malekzadeh, Reza; Mangalam, Srikanth; Mapoma, Christopher C; Marape, Marape; Marcenes, Wagner; Margolis, David J; Margono, Christopher; Marks, Guy B; Martin, Randall V; Marzan, Melvin B; Mashal, Mohammad T; Masiye, Felix; Mason-Jones, Amanda J; Matsushita, Kunihiro; Matzopoulos, Richard; Mayosi, Bongani M; Mazorodze, Tasara T; McKay, Abigail C; McKee, Martin; McLain, Abigail; Meaney, Peter A; Medina, Catalina; Mehndiratta, Man Mohan; Mejia-Rodriguez, Fabiola; Mekonnen, Wubegzier; Melaku, Yohannes A; Meltzer, Michele; Memish, Ziad A; Mendoza, Walter; Mensah, George A; Meretoja, Atte; Mhimbira, Francis Apolinary; Micha, Renata; Miller, Ted R; Mills, Edward J; Misganaw, Awoke; Mishra, Santosh; Mohamed Ibrahim, Norlinah; Mohammad, Karzan A; Mokdad, Ali H; Mola, Glen L; Monasta, Lorenzo; Montanez Hernandez, Julio C; Montico, Marcella; Moore, Ami R; Morawska, Lidia; Mori, Rintaro; Moschandreas, Joanna; Moturi, Wilkister N; Mozaffarian, Dariush; Mueller, Ulrich O; Mukaigawara, Mitsuru; Mullany, Erin C; Murthy, Kinnari S; Naghavi, Mohsen; Nahas, Ziad; Naheed, Aliya; Naidoo, Kovin S; Naldi, Luigi; Nand, Devina; Nangia, Vinay; Narayan, K M Venkat; Nash, Denis; Neal, Bruce; Nejjari, Chakib; Neupane, Sudan P; Newton, Charles R; Ngalesoni, Frida N; Ngirabega, Jean de Dieu; Nguyen, Grant; Nguyen, Nhung T; Nieuwenhuijsen, Mark J; Nisar, Muhammad I; Nogueira, Jose R; Nolla, Joan M; Nolte, Sandra; Norheim, Ole F; Norman, Rosana E; Norrving, Bo; Nyakarahuka, Luke; Oh, In-Hwan; Ohkubo, Takayoshi; Olusanya, Bolajoko O; Omer, Saad B; Opio, John Nelson; Orozco, Ricardo; Pagcatipunan, Rodolfo S Jr; Pain, Amanda W; Pandian, Jeyaraj D; Panelo, Carlo Irwin A; Papachristou, Christina; Park, Eun-Kee; Parry, Charles D; Paternina Caicedo, Angel J; Patten, Scott B; Paul, Vinod K; Pavlin, Boris I; Pearce, Neil; Pedraza, Lilia S; Pedroza, Andrea; Pejin Stokic, Ljiljana; Pekericli, Ayfer; Pereira, David M; Perez-Padilla, Rogelio; Perez-Ruiz, Fernando; Perico, Norberto; Perry, Samuel A L; Pervaiz, Aslam; Pesudovs, Konrad; Peterson, Carrie B; Petzold, Max; Phillips, Michael R; Phua, Hwee Pin; Plass, Dietrich; Poenaru, Dan; Polanczyk, Guilherme V; Polinder, Suzanne; Pond, Constance D; Pope, C Arden; Pope, Daniel; Popova, Svetlana; Pourmalek, Farshad; Powles, John; Prabhakaran, Dorairaj; Prasad, Noela M; Qato, Dima M; Quezada, Amado D; Quistberg, D Alex A; Racape, Lionel; Rafay, Anwar; Rahimi, Kazem; Rahimi-Movaghar, Vafa; Rahman, Sajjad Ur; Raju, Murugesan; Rakovac, Ivo; Rana, Saleem M; Rao, Mayuree; Razavi, Homie; Reddy, K Srinath; Refaat, Amany H; Rehm, Jurgen; Remuzzi, Giuseppe; Ribeiro, Antonio L; Riccio, Patricia M; Richardson, Lee; Riederer, Anne; Robinson, Margaret; Roca, Anna; Rodriguez, Alina; Rojas-Rueda, David; Romieu, Isabelle; Ronfani, Luca; Room, Robin; Roy, Nobhojit; Ruhago, George M; Rushton, Lesley; Sabin, Nsanzimana; Sacco, Ralph L; Saha, Sukanta; Sahathevan, Ramesh; Sahraian, Mohammad Ali; Salomon, Joshua A; Salvo, Deborah; Sampson, Uchechukwu K; Sanabria, Juan R; Sanchez, Luz Maria; Sanchez-Pimienta, Tania G; Sanchez-Riera, Lidia; Sandar, Logan; Santos, Itamar S; Sapkota, Amir; Satpathy, Maheswar; Saunders, James E; Sawhney, Monika; Saylan, Mete I; Scarborough, Peter; Schmidt, Jurgen C; Schneider, Ione J C; Schottker, Ben; Schwebel, David C; Scott, James G; Seedat, Soraya; Sepanlou, Sadaf G; Serdar, Berrin; Servan-Mori, Edson E; Shaddick, Gavin; Shahraz, Saeid; Levy, Teresa Shamah; Shangguan, Siyi; She, Jun; Sheikhbahaei, Sara; Shibuya, Kenji; Shin, Hwashin H; Shinohara, Yukito; Shiri, Rahman; Shishani, Kawkab; Shiue, Ivy; Sigfusdottir, Inga D; Silberberg, Donald H; Simard, Edgar P; Sindi, Shireen; Singh, Abhishek; Singh, Gitanjali M; Singh, Jasvinder A; Skirbekk, Vegard; Sliwa, Karen; Soljak, Michael; Soneji, Samir; Soreide, Kjetil; Soshnikov, Sergey; Sposato, Luciano A; Sreeramareddy, Chandrashekhar T; Stapelberg, Nicolas J C; Stathopoulou, Vasiliki; Steckling, Nadine; Stein, Dan J; Stein, Murray B; Stephens, Natalie; Stockl, Heidi; Straif, Kurt; Stroumpoulis, Konstantinos; Sturua, Lela; Sunguya, Bruno F; Swaminathan, Soumya; Swaroop, Mamta; Sykes, Bryan L; Tabb, Karen M; Takahashi, Ken; Talongwa, Roberto T; Tandon, Nikhil; Tanne, David; Tanner, Marcel; Tavakkoli, Mohammad; Te Ao, Braden J; Teixeira, Carolina M; Tellez Rojo, Martha M; Terkawi, Abdullah S; Texcalac-Sangrador, Jose Luis; Thackway, Sarah V; Thomson, Blake; Thorne-Lyman, Andrew L; Thrift, Amanda G; Thurston, George D; Tillmann, Taavi; Tobollik, Myriam; Tonelli, Marcello; Topouzis, Fotis; Towbin, Jeffrey A; Toyoshima, Hideaki; Traebert, Jefferson; Tran, Bach X; Trasande, Leonardo; Trillini, Matias; Trujillo, Ulises; Dimbuene, Zacharie Tsala; Tsilimbaris, Miltiadis; Tuzcu, Emin Murat; Uchendu, Uche S; Ukwaja, Kingsley N; Uzun, Selen B; van de Vijver, Steven; Van Dingenen, Rita; van Gool, Coen H; van Os, Jim; Varakin, Yuri Y; Vasankari, Tommi J; Vasconcelos, Ana Maria N; Vavilala, Monica S; Veerman, Lennert J; Velasquez-Melendez, Gustavo; Venketasubramanian, N; Vijayakumar, Lakshmi; Villalpando, Salvador; Violante, Francesco S; Vlassov, Vasiliy Victorovich; Vollset, Stein Emil; Wagner, Gregory R; Waller, Stephen G; Wallin, Mitchell T; Wan, Xia; Wang, Haidong; Wang, JianLi; Wang, Linhong; Wang, Wenzhi; Wang, Yanping; Warouw, Tati S; Watts, Charlotte H; Weichenthal, Scott; Weiderpass, Elisabete; Weintraub, Robert G; Werdecker, Andrea; Wessells, K Ryan; Westerman, Ronny; Whiteford, Harvey A; Wilkinson, James D; Williams, Hywel C; Williams, Thomas N; Woldeyohannes, Solomon M; Wolfe, Charles D A; Wong, John Q; Woolf, Anthony D; Wright, Jonathan L; Wurtz, Brittany; Xu, Gelin; Yan, Lijing L; Yang, Gonghuan; Yano, Yuichiro; Ye, Pengpeng; Yenesew, Muluken; Yentur, Gokalp K; Yip, Paul; Yonemoto, Naohiro; Yoon, Seok-Jun; Younis, Mustafa Z; Younoussi, Zourkaleini; Yu, Chuanhua; Zaki, Maysaa E; Zhao, Yong; Zheng, Yingfeng; Zhou, Maigeng; Zhu, Jun; Zhu, Shankuan; Zou, Xiaonong; Zunt, Joseph R; Lopez, Alan D; Vos, Theo; Murray, Christopher J
BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. FINDINGS: All risks combined account for 57.2% (95% uncertainty interval [UI] 55.8-58.5) of deaths and 41.6% (40.1-43.0) of DALYs. Risks quantified account for 87.9% (86.5-89.3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11.3 million deaths and 241.4 million DALYs, high systolic blood pressure for 10.4 million deaths and 208.1 million DALYs, child and maternal malnutrition for 1.7 million deaths and 176.9 million DALYs, tobacco smoke for 6.1 million deaths and 143.5 million DALYs, air pollution for 5.5 million deaths and 141.5 million DALYs, and high BMI for 4.4 million deaths and 134.0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. FUNDING: Bill & Melinda Gates Foundation.
PMCID:4685753
PMID: 26364544
ISSN: 1474-547x
CID: 2033272
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types
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; De Vivo, 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, Chih-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, Francoise; 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; Foretova, Lenka; Fraumeni, Joseph F Jr; Freedman, Neal D; Beane Freeman, Laura E; 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 3rd; 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 3rd; 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, Chang Hyun; 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, Yuqing; Liao, Linda M; Liebow, Mark; Lightfoot, Tracy; Lim, Wei-Yen; Lin, Chien-Chung; Lin, Dongxin; Lindstrom, Sara; Linet, Martha S; Link, Brian K; Liu, Chenwei; Liu, Jianjun; Liu, Li; Ljungberg, Borje; 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-Il; 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
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 (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.
PMCID:4806328
PMID: 26464424
ISSN: 1460-2105
CID: 1909402