Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3.
Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3.
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作者：
我们在来自11项研究的3，772例欧洲背景的病例和8，505例对照中进行了肾细胞癌（RCC）的两阶段全基因组关联研究，并在2，198例病例和4，918例对照的三项重复研究中随访了6个SNP。位于2 p21和11q13.3区域的两个位点与肾癌易感性的相关性低于全基因组显著性。两个相关的变体（对照组中r2 = 0.99），rs 11894252（P = 1.8×10−8）和rs7579899（P = 2.3×10−9），映射到2 p21上的EPAS 1，该基因编码低氧诱导因子-2 α，这是一种先前与RCC有关的转录因子。第二个基因座rs7105934位于11 q13，不包含特征基因（P = 7.8×10−14）。此外，我们观察到rs 4765623在12 q24.31上的有希望的关联，该关联映射到清道夫受体B类成员1（SCARB 1）基因（P = 2.6×10−8）。我们的研究报告了与RCC风险相关的新基因组区域，这可能导致新的病因学见解。
We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 cases and 8,505 controls of European background from 11 studies, and followed up 6 SNPs in three replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r2 = 0.99 in controls), rs11894252 (P = 1.8×10−8) and rs7579899 (P = 2.3×10−9), map to EPAS1 on 2p21, which encodes hypoxia-inducible- factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13, contains no characterized genes (P = 7.8×10−14). In addition, we observed a promising association on 12q24.31 for rs4765623 which maps to the scavenger receptor class B, member 1 (SCARB1) gene (P = 2.6×10−8). Our study reports novel genomic regions associated with RCC risk that may lead to new etiological insights.
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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
3.5
作者：
de Bakker, Paul I. W.;Ferreira, Manuel A. R.;Voight, Benjamin F.
通讯作者：
Voight, Benjamin F.
影响因子：
6.2
作者：
Linehan WM;Pinto PA;Bratslavsky G;Pfaffenroth E;Merino M;Vocke CD;Toro JR;Bottaro D;Neckers L;Schmidt LS;Srinivasan R
通讯作者：
Srinivasan R
影响因子：
30.8
作者：
Eeles, Rosalind A.;Kote-Jarai, Zsofia;Easton, Douglas F.
通讯作者：
Easton, Douglas F.
影响因子：
64.8
作者：
Altshuler, David;Durbin, Richard M.;Abecasis, Goncalo R.;Bentley, David R.;Chakravarti, Aravinda;Clark, Andrew G.;Collins, Francis S.;De la Vega, Francisco M.;Donnelly, Peter;Egholm, Michael;Flicek, Paul;Gabriel, Stacey B.;Gibbs, Richard A.;Knoppers, Bartha M.;Lander, Eric S.;Lehrach, Hans;Mardis, Elaine R.;McVean, Gil A.;Nickerson, DebbieA.;Peltonen, Leena;Schafer, Alan J.;Sherry, Stephen T.;Wang, Jun;Wilson, Richard K.;Gibbs, Richard A.;Deiros, David;Metzker, Mike;Muzny, Donna;Reid, Jeff;Wheeler, David;Wang, Jun;Li, Jingxiang;Jian, Min;Li, Guoqing;Li, Ruiqiang;Liang, Huiqing;Tian, Geng;Wang, Bo;Wang, Jian;Wang, Wei;Yang, Huanming;Zhang, Xiuqing;Zheng, Huisong;Lander, Eric S.;Altshuler, David L.;Ambrogio, Lauren;Bloom, Toby;Cibulskis, Kristian;Fennell, Tim J.;Gabriel, Stacey B.;Jaffe, David B.;Shefler, Erica;Sougnez, Carrie L.;Bentley, David R.;Gormley, Niall;Humphray, Sean;Kingsbury, Zoya;Koko-Gonzales, Paula;Stone, Jennifer;McKernan, Kevin J.;Costa, Gina L.;Ichikawa, Jeffry K.;Lee, Clarence C.;Sudbrak, Ralf;Lehrach, Hans;Borodina, Tatiana A.;Dahl, Andreas;Davydov, Alexey N.;Marquardt, Peter;Mertes, Florian;Nietfeld, Wilfiried;Rosenstiel, Philip;Schreiber, Stefan;Soldatov, Aleksey V.;Timmermann, Bernd;Tolzmann, Marius;Egholm, Michael;Affourtit, Jason;Ashworth, Dana;Attiya, Said;Bachorski, Melissa;Buglione, Eli;Burke, Adam;Caprio, Amanda;Celone, Christopher;Clark, Shauna;Conners, David;Desany, Brian;Gu, Lisa;Guccione, Lorri;Kao, Kalvin;Kebbel, Andrew;Knowlton, Jennifer;Labrecque, Matthew;McDade, Louise;Mealmaker, Craig;Minderman, Melissa;Nawrocki, Anne;Niazi, Faheem;Pareja, Kristen;Ramenani, Ravi;Riches, David;Song, Wanmin;Turcotte, Cynthia;Wang, Shally;Mardis, Elaine R.;Dooling, David;Fulton, Lucinda;Fulton, Robert;Weinstock, George;Durbin, Richard M.;Burton, John;Carter, David M.;Churcher, Carol;Coffey, Alison;Cox, Anthony;Palotie, Aarno;Quail, Michael;Skelly, Tom;Stalker, James;Swerdlow, Harold P.;Turner, Daniel;De Witte, Anniek;Giles, Shane;Gibbs, Richard A.;Wheeler, David;Bainbridge, Matthew;Challis, Danny;Sabo, Aniko;Yu, Fuli;Yu, Jin;Wang, Jun;Fang, Xiaodong;Guo, Xiaosen;Li, Ruiqiang;Li, Yingrui;Luo, Ruibang;Tai, Shuaishuai;Wu, Honglong;Zheng, Hancheng;Zheng, Xiaole;Zhou, Yan;Yang, Huanming;Marth, Gabor T.;Garrison, Erik P.;Huang, Weichun;Indap, Amit;Kural, Deniz;Lee, Wan-Ping;Leong, Wen Fung;Huang, Weichun;Indap, Amit;Kural, Deniz;Lee, Wan-Ping;Leong, Wen Fung;Quinlan, Aaron R.;Stewart, Chip;Stromberg, Michael P.;Ward, Alistair N.;Wu, Jiantao;Lee, Charles;Mills, Ryan E.;Shi, Xinghua;Daly, Mark J.;DePristo, Mark A.;Altshuler, David L.;Ball, Aaron D.;Banks, Eric;Bloom, Toby;Browning, Brian L.;Cibulskis, Kristian;Fennell, Tim J.;Garimella, Kiran V.;Grossman, Sharon R.;Handsaker, Robert E.;Hanna, Matt;Hartl, Chris;Jaffe, David B.;Kernytsky, Andrew M.;Korn, Joshua M.;Li, Heng;Maguire, Jared R.;McCarroll, Steven A.;McKenna, Aaron;Nemesh, James C.;Philippakis, Anthony A.;Poplin, Ryan E.;Price, Alkes;Rivas, Manuel A.;Sabeti, Pardis C.;Schaffner, Stephen F.;Shefler, Erica;Shlyakhter, Ilya A.;Cooper, David N.;Ball, Edward V.;Mort, Matthew;Phillips, Andrew D.;Stenson, Peter D.;Sebat, Jonathan;Makarov, Vladimir;Ye, Kenny;Yoon, Seungtai C.;Bustamante, Carlos D.;Clark, Andrew G.;Boyko, Adam;Degenhardt, Jeremiah;Gravel, Simon;Gutenkunst, Ryan N.;Kaganovich, Mark;Keinan, Alon;Lacroute, Phil;Ma, Xia;Reynolds, Andy;Clarke, Laura;Flicek, Paul;Cunningham, Fiona;Herrero, Javier;Keenen, Stephen;Kulesha, Eugene;Leinonen, Rasko;McLaren, WilliamM.;Radhakrishnan, Rajesh;Smith, Richard E.;Zalunin, Vadim;Zheng-Bradley, Xiangqun;Korbel, Jan O.;Stuetz, Adrian M.;Humphray, Sean;Bauer, Markus;Cheetham, R. Keira;Cox, Tony;Eberle, Michael;James, Terena;Kahn, Scott;Murray, Lisa;Ye, Kai;De La Vega, Francisco M.;Fu, Yutao;Hyland, Fiona C. L.;Manning, Jonathan M.;McLaughlin, Stephen F.;Peckham, Heather E.;Sakarya, Onur;Sun, Yongming A.;Tsung, Eric F.;Batzer, Mark A.;Konkel, Miriam K.;Walker, Jerilyn A.;Sudbrak, Ralf;Albrecht, Marcus W.;Amstislavskiy, Vyacheslav S.;Herwig, Ralf;Parkhomchuk, Dimitri V.;Sherry, Stephen T.;Agarwala, Richa;Khouri, Hodam.;Morgulis, Aleksandr O.;Paschall, Justin E.;Phan, Lon D.;Rotmistrovsky, Kirill E.;Sanders, Robert D.;Shumway, Martin F.;Xiao, Chunlin;McVean, Gil A.;Auton, Adam;Iqbal, Zamin;Lunter, Gerton;Marchini, Jonathan L.;Moutsianas, Loukas;Myers, Simon;Tumian, Afidalina;Desany, Brian;Knight, James;Winer, Roger;Craig, David W.;Beckstrom-Sternberg, Steve M.;Christoforides, Alexis;Kurdoglu, Ahmet A.;Pearson, Johnv.;Sinari, Shripad A.;Tembe, Waibhav D.;Haussler, David;Hinrichs, Angie S.;Katzman, Sol J.;Kern, Andrew;Kuhn, Robert M.;Przeworski, Molly;Hernandez, Ryan D.;Howie, Bryan;Kelley, Joanna L.;Melton, S. Cord;Abecasis, Goncalo R.;Li, Yun;Anderson, Paul;Blackwell, Tom;Chen, Wei;Cookson, William O.;Ding, Jun;Kang, Hyun Min;Lathrop, Mark;Liang, Liming;Moffatt, Miriam F.;Scheet, Paul;Sidore, Carlo;Snyder, Matthew;Zhan, Xiaowei;Zoellner, Sebastian;Awadalla, Philip;Casals, Ferran;Idaghdour, Youssef;Keebler, John;Stone, Eric A.;Zilversmit, Martine;Jorde, Lynn;Xing, Jinchuan;Eichler, Evan E.;Aksay, Gozde;Alkan, Can;Hajirasouliha, Iman;Hormozdiari, Fereydoun;Kidd, Jeffrey M.;Sahinalp, S. Cenk;Sudmant, Peter H.;Mardis, Elaine R.;Chen, Ken;Chinwalla, Asif;Ding, Li;Koboldt, Daniel C.;McLellan, Mike D.;Dooling, David;Weinstock, George;Wallis, John W.;Wendl, Michael C.;Zhang, Qunyuan;Durbin, Richard M.;Albers, Cornelis A.;Ayub, Qasim;Balasubramaniam, Senduran;Barrett, Jeffrey C.;Carter, David M.;Chen, Yuan;Conrad, Donald F.;Danecek, Petr;Dermitzakis, Emmanouil T.;Hu, Min;Huang, Ni;Hurles, Matt E.;Jin, Hanjun;Jostins, Luke;Keane, Thomas M.;Keane, Thomas M.;Le, Si Quang;Lindsay, Sarah;Long, Quan;MacArthur, Daniel G.;Montgomery, Stephen B.;Parts, Leopold;Stalker, James;Tyler-Smith, Chris;Walter, Klaudia;Zhang, Yujun;Gerstein, Mark B.;Snyder, Michael;Abyzov, Alexej;Abyzov, Alexej;Balasubramanian, Suganthi;Bjornson, Robert;Du, Jiang;Grubert, Fabian;Habegger, Lukas;Haraksingh, Rajini;Jee, Justin;Khurana, Ekta;Lam, Hugo Y. K.;Leng, Jing;Mu, Xinmeng Jasmine;Urban, Alexander E.;Zhang, Zhengdong;Li, Yingrui;Luo, Ruibang;Marth, Gabor T.;Garrison, Erik P.;Kural, Deniz;Quinlan, Aaron R.;Stewart, Chip;Stromberg, Michael P.;Ward, Alistair N.;Wu, Jiantao;Lee, Charles;Mills, Ryan E.;Shi, Xinghua;McCarroll, Steven A.;Banks, Eric;DePristo, Mark A.;Handsaker, Robert E.;Hartl, Chris;Korn, Joshua M.;Li, Heng;Nemesh, James C.;Sebat, Jonathan;Makarov, Vladimir;Ye, Kenny;Yoon, Seungtai C.;Degenhardt, Jeremiah;Kaganovich, Mark;Clarke, Laura;Smith, Richard E.;Zheng-Bradley, Xiangqun;Korbel, Jan O.;Humphray, Sean;Cheetham, R. Keira;Eberle, Michael;Kahn, Scott;Murray, Lisa;Ye, Kai;De la Vega, Francisco M.;Fu, Yutao;Peckham, Heather E.;Sun, Yongming A.;Batzer, Mark A.;Konkel, Miriam K.;Xiao, Chunlin;Iqbal, Zamin;Desany, Brian;Blackwell, Tom;Snyder, Matthew;Xing, Jinchuan;Eichler, Evan E.;Aksay, Gozde;Alkan, Can;Hajirasouliha, Iman;Hormozdiari, Fereydoun;Kidd, Jeffrey M.;Chen, Ken;Chinwalla, Asif;Ding, Li;McLellan, Mike D.;Wallis, John W.;Hurles, Matt E.;Conrad, Donald F.;Walter, Klaudia;Zhang, Yujun;Gerstein, Mark B.;Snyder, Michael;Abyzov, Alexej;Du, Jiang;Grubert, Fabian;Haraksingh, Rajini;Jee, Justin;Khurana, Ekta;Lam, Hugo Y. K.;Leng, Jing;Mu, Xinmeng Jasmine;Urban, Alexander E.;Zhang, Zhengdong;Gibbs, Richard A.;Bainbridge, Matthew;Challis, Danny;Coafra, Cristian;Dinh, Huyen;Kovar, Christie;Lee, Sandy;Muzny, Donna;Nazareth, Lynne;Reid, Jeff;Sabo, Aniko;Yu, Fuli;Yu, Jin;Marth, Gabor T.;Garrison, Erik P.;Indap, Amit;Leong, Wen Fung;Quinlan, Aaron R.;Stewart, Chip;Ward, Alistair N.;Wu, Jiantao;Cibulskis, Kristian;Fennell, Tim J.;Gabriel, Stacey B.;Garimella, Kiran V.;Hartl, Chris;Shefler, Erica;Sougnez, Carrie L.;Wilkinson, Jane;Clark, Andrew G.;Gravel, Simon;Grubert, Fabian;Clarke, Laura;Flicek, Paul;Smith, Richard E.;Zheng-Bradley, Xiangqun;Sherry, Stephen T.;Khouri, Hoda M.;Paschall, Justin E.;Shumway, Martin F.;Xiao, Chunlin;McVean, Gil A.;Katzman, Sol J.;Abecasis, Goncalo R.;Blackwell, Tom;Mardis, Elaine R.;Dooling, David;Fulton, Lucinda;Fulton, Robert;Koboldt, Daniel C.;Durbin, Richard M.;Balasubramaniam, Senduran;Coffey, Allison;Keane, Thomas M.;MacArthur, Daniel G.;Palotie, Aarno;Scott, Carol;Stalker, James;Tyler-Smith, Chris;Gerstein, Mark B.;Balasubramanian, Suganthi;Chakravarti, Aravinda;Knoppers, Bartha M.;Peltonen, Leena;Abecasis, Goncalo R.;Bustamante, Carlos D.;Gharani, Neda;Gibbs, Richard A.;Jorde, Lynn;Kaye, Jane S.;Kent, Alastair;Li, Taosha;McGuire, Amy L.;McVean, Gil A.;Ossorio, Pilar N.;Rotimi, Charles N.;Su, Yeyang;Toji, Lorraine H.;Tyler-Smith, Chris;Brooks, Lisa D.;Felsenfeld, Adam L.;McEwen, Jean E.;Abdallah, Assya;Juenger, Christopher R.;Clemm, Nicholas C.;Collins, Francis S.;Duncanson, Audrey;Green, Eric D.;Guyer, Mark S.;Peterson, Jane L.;Schafer, Alan J.;Abecasis, Goncalo R.;Altshuler, David L.;Auton, Adam;Brooks, Lisa D.;Durbin, Richard M.;Gibbs, Richard A.;Hurles, Matt E.;McVean, Gil A.
通讯作者：
McVean, Gil A.