Prediction of individual genetic risk to prostate cancer using a polygenic score.
Prediction of individual genetic risk to prostate cancer using a polygenic score.
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使用多基因评分预测前列腺癌的个体遗传风险。
DOI：
10.1002/pros.23037
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Wiklund F
中科院分区：
文献类型：
--
作者：
Szulkin R;Whitington T;Eklund M;Aly M;Eeles RA;Easton D;Kote-Jarai ZS;Amin Al Olama A;Benlloch S;Muir K;Giles GG;Southey MC;Fitzgerald LM;Henderson BE;Schumacher F;Haiman CA;Schleutker J;Wahlfors T;Tammela TL;Nordestgaard BG;Key TJ;Travis RC;Neal DE;Donovan JL;Hamdy FC;Pharoah P;Pashayan N;Khaw KT;Stanford JL;Thibodeau SN;McDonnell SK;Schaid DJ;Maier C;Vogel W;Luedeke M;Herkommer K;Kibel AS;Cybulski C;Lubiński J;Kluźniak W;Cannon-Albright L;Brenner H;Butterbach K;Stegmaier C;Park JY;Sellers T;Lin HY;Slavov C;Kaneva R;Mitev V;Batra J;Clements JA;Australian Prostate Cancer BioResource;Spurdle A;Teixeira MR;Paulo P;Maia S;Pandha H;Michael A;Kierzek A;Practical Consortium;Gronberg H;Wiklund F
多基因风险评分包括已建立的易感性变异已被证明是几个复杂的疾病，包括前列腺癌的信息分类。对于前列腺癌，目前尚不清楚是否包括迄今为止尚未在全基因组显著水平上与前列腺癌风险相关的遗传标记将改善疾病预测。我们在一个由超过25，000人组成的大型训练集中建立了多基因风险评分。最初选择了65种已建立的前列腺癌易感性变体。在LD修剪之后，基于它们与前列腺癌的关联对另外的变体进行优先级排序。进行六重交叉验证以评估遗传风险评分并优化待纳入的额外变体的数量。最终模型在包括1，370例病例和1，239例对照的独立研究人群中进行了评价。多基因风险评分与65个已建立的易感性变异提供了0.67的曲线下面积（AUC）。添加额外的68种新变体使AUC显著增加至0.68（P = 0.0012），净重新分类指数显著增加至0.21（P = 8.5 E-08）。所有新的变异都位于与前列腺癌风险相关的基因组区域。纳入来自已建立的前列腺癌易感区域的额外遗传变异可改善疾病预测。
Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5 E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction.
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影响因子：
2
作者：
Pencina, Michael J.;D'Agostino, Ralph B., Sr.;Steyerberg, Ewout W.
通讯作者：
Steyerberg, Ewout W.
影响因子：
8.8
作者：
Janssens, A. Cecile J. W.;Moonesinghe, Ramal;Khoury, Muin J.
通讯作者：
Khoury, Muin J.
影响因子：
8.8
作者：
Leongamornlert, D.;Mahmud, N.;Tymrakiewicz, M.;Saunders, E.;Dadaev, T.;Castro, E.;Goh, C.;Govindasami, K.;Guy, M.;O'Brien, L.;Sawyer, E.;Hall, A.;Wilkinson, R.;Easton, D.;Goldgar, D.;Eeles, R.;Kote-Jarai, Z.
通讯作者：
Kote-Jarai, Z.
DOI：
10.1158/1055-9965.epi-11-1038
发表时间：
2012-03
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Lindström S;Schumacher FR;Cox D;Travis RC;Albanes D;Allen NE;Andriole G;Berndt SI;Boeing H;Bueno-de-Mesquita HB;Crawford ED;Diver WR;Gaziano JM;Giles GG;Giovannucci E;Gonzalez CA;Henderson B;Hunter DJ;Johansson M;Kolonel LN;Ma J;Le Marchand L;Pala V;Stampfer M;Stram DO;Thun MJ;Tjonneland A;Trichopoulos D;Virtamo J;Weinstein SJ;Willett WC;Yeager M;Hayes RB;Severi G;Haiman CA;Chanock SJ;Kraft P
通讯作者：
Kraft P
影响因子：
30.8
作者：
Eeles, Rosalind A.;Al Olama, Ali Amin;Benlloch, Sara;Saunders, Edward J.;Leongamornlert, Daniel A.;Tymrakiewicz, Malgorzata;Ghoussaini, Maya;Luccarini, Craig;Dennis, Joe;Jugurnauth-Little, Sarah;Dadaev, Tokhir;Neal, David E.;Hamdy, Freddie C.;Donovan, Jenny L.;Muir, Ken;Giles, Graham G.;Severi, Gianluca;Wiklund, Fredrik;Gronberg, Henrik;Haiman, Christopher A.;Schumacher, Fredrick;Henderson, Brian E.;Le Marchand, Loic;Lindstrom, Sara;Kraft, Peter;Hunter, David J.;Gapstur, Susan;Chanock, Stephen J.;Berndt, Sonja I.;Albanes, Demetrius;Andriole, Gerald;Schleutker, Johanna;Weischer, Maren;Canzian, Federico;Riboli, Elio;Key, Tim J.;Travis, Ruth C.;Campa, Daniele;Ingles, Sue A.;John, Esther M.;Hayes, Richard B.;Pharoah, Paul D. P.;Pashayan, Nora;Khaw, Kay-Tee;Stanford, Janet L.;Ostrander, Elaine A.;Signorello, Lisa B.;Thibodeau, Stephen N.;Schaid, Dan;Maier, Christiane;Vogel, Walther;Kibel, Adam S.;Cybulski, Cezary;Lubhiski, Jan;Cannon-Albright, Lisa;Brenner, Hermann;Park, Jong Y.;Kaneva, Radka;Batra, Jyotsna;Spurdle, Amanda B.;Clements, Judith A.;Teixeira, Manuel R.;Dicks, Ed;Lee, Andrew;Dunning, Alison M.;Baynes, Caroline;Conroy, Don;Maranian, Melanie J.;Ahmed, Shahana;Govindasami, Koveela;Guy, Michelle;Wilkinson, Rosemary A.;Sawyer, Emma J.;Morgan, Angela;Dearnaley, David P.;Horwich, Alan;Huddart, Robert A.;Khoo, Vincent S.;Parker, Christopher C.;Van As, Nicholas J.;Woodhouse, Christopher J.;Thompson, Alan;Dudderidge, Tim;Ogden, Chris;Cooper, Colin S.;Lophatananon, Artitaya;Cox, Angela;Southey, Melissa C.;Hopper, John L.;English, Dallas R.;Aly, Markus;Adolfsson, Jan;Xu, Jiangfeng;Zheng, Siqun L.;Yeager, Meredith;Kaaks, Rudolf;Diver, W. Ryan;Gaudet, Mia M.;Stern, Mariana C.;Corral, Roman;Joshi, Amit D.;Shahabi, Ahva;Wahlfors, Tiina;Tammela, Teuvo L. J.;Auvinen, Anssi;Virtamo, Jarmo;Klarskov, Peter;Nordestgaard, Borge G.;Roder, M. Andreas;Nielsen, Sune F.;Bojesen, Stig E.;Siddiq, Afshan;FitzGerald, Liesel M.;Kolb, Suzanne;Kwon, Erika M.;Karyadi, Danielle M.;Blot, William J.;Zheng, Wei;Cai, Qiuyin;McDonnell, Shannon K.;Rinckleb, Antje E.;Drake, Bettina;Colditz, Graham;Wokolorczyk, Dominika;Stephenson, Robert A.;Teerlink, Craig;Muller, Heiko;Rothenbacher, Dietrich;Sellers, Thomas A.;Lin, Hui-Yi;Slavov, Chavdar;Mitev, Vanio;Lose, Felicity;Srinivasan, Srilakshmi;Maia, Sofia;Paulo, Paula;Lange, Ethan;Cooney, Kathleen A.;Antoniou, Antonis C.;Vincent, Daniel;Bacot, Francois;Tessier, Daniel C.;Kote-Jarai, Zsofia;Easton, Douglas F.
通讯作者：
Easton, Douglas F.