Genomic prediction of coronary heart disease.
Genomic prediction of coronary heart disease.
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DOI：
10.1093/eurheartj/ehw450
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发表时间：
2016-11-14
影响因子：
39.3
通讯作者：
Inouye M
中科院分区：
文献类型：
--
作者：
Abraham G;Havulinna AS;Bhalala OG;Byars SG;De Livera AM;Yetukuri L;Tikkanen E;Perola M;Schunkert H;Sijbrands EJ;Palotie A;Samani NJ;Salomaa V;Ripatti S;Inouye M
遗传学在冠心病(CHD)中起着重要作用，但基因组风险评分(GRS)相对于临床风险评分(如Framingham风险评分(FRS))的临床实用性尚不清楚。我们的目标是构建和外部验证CHD GRS，根据终生CHD风险和相对于传统临床风险评分。我们基于CARDIoGRAMplusC4D联盟对冠心病的荟萃分析生成了49个 310 SNPs，然后使用五个前瞻性人群队列(三个FINRISK队列，合并n = 12 676,757个冠心病事件；两个Framingham心脏研究队列，合并n = 3406,587个冠心病事件)进行独立测试。GRS与冠心病事件相关(FINRISK HR = 1.74，95%可信区间(CI)1.61-1.86/SD；Framingham HR = 1.28，95%CI 1.18-1.38)，在调整包括家族史在内的已知危险因素后，GRS基本不变。将GRS与FRS或Acc/AHA13评分相结合改善了10年风险预测(Meta分析C指数： +1.5%-1.6%，P <； 0.001)，特别是对60岁的个体(Meta分析C指数： ≥ +4.6%-5.1%，P <； 0.001)。重要的是，GRS捕捉到了截然不同的绝对风险轨迹，排名前20%的男性获得累积冠心病风险10%的时间比排名后20%的男性早12-18年。低收缩压、低胆固醇水平和非吸烟可以部分补偿高基因组风险。基于大量SNPs的GRS改进了CHD风险预测，并编码了传统临床风险评分无法涵盖的不同终生风险轨迹。
Genetics plays an important role in coronary heart disease (CHD) but the clinical utility of genomic risk scores (GRSs) relative to clinical risk scores, such as the Framingham Risk Score (FRS), is unclear. Our aim was to construct and externally validate a CHD GRS, in terms of lifetime CHD risk and relative to traditional clinical risk scores. We generated a GRS of 49 310 SNPs based on a CARDIoGRAMplusC4D Consortium meta-analysis of CHD, then independently tested it using five prospective population cohorts (three FINRISK cohorts, combined n = 12 676, 757 incident CHD events; two Framingham Heart Study cohorts (FHS), combined n = 3406, 587 incident CHD events). The GRS was associated with incident CHD (FINRISK HR = 1.74, 95% confidence interval (CI) 1.61–1.86 per S.D. of GRS; Framingham HR = 1.28, 95% CI 1.18–1.38), and was largely unchanged by adjustment for known risk factors, including family history. Integration of the GRS with the FRS or ACC/AHA13 scores improved the 10 years risk prediction (meta-analysis C-index: +1.5–1.6%, P < 0.001), particularly for individuals ≥60 years old (meta-analysis C-index: +4.6–5.1%, P < 0.001). Importantly, the GRS captured substantially different trajectories of absolute risk, with men in the top 20% of attaining 10% cumulative CHD risk 12–18 y earlier than those in the bottom 20%. High genomic risk was partially compensated for by low systolic blood pressure, low cholesterol level, and non-smoking. A GRS based on a large number of SNPs improves CHD risk prediction and encodes different trajectories of lifetime risk not captured by traditional clinical risk scores.
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DOI：
10.1056/nejmoa072366
发表时间：
2007-08-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Samani NJ;Erdmann J;Hall AS;Hengstenberg C;Mangino M;Mayer B;Dixon RJ;Meitinger T;Braund P;Wichmann HE;Barrett JH;König IR;Stevens SE;Szymczak S;Tregouet DA;Iles MM;Pahlke F;Pollard H;Lieb W;Cambien F;Fischer M;Ouwehand W;Blankenberg S;Balmforth AJ;Baessler A;Ball SG;Strom TM;Braenne I;Gieger C;Deloukas P;Tobin MD;Ziegler A;Thompson JR;Schunkert H;WTCCC and the Cardiogenics Consortium
通讯作者：
WTCCC and the Cardiogenics Consortium
影响因子：
158.5
作者：
Florez, Jose C.;Jablonski, Kathleen A.;Altshuler, David
通讯作者：
Altshuler, David
影响因子：
30.8
作者：
Deloukas, Panos;Kanoni, Stavroula;Willenborg, Christina;Farrall, Martin;Assimes, Themistocles L.;Thompson, John R.;Ingelsson, Erik;Saleheen, Danish;Erdmann, Jeanette;Goldstein, Benjamin A.;Stirrups, Kathleen;Koenig, Inke R.;Cazier, Jean-Baptiste;Johansson, Asa;Hall, Alistair S.;Lee, Jong-Young;Willer, Cristen J.;Chambers, John C.;Esko, Tonu;Folkersen, Lasse;Goel, Anuj;Grundberg, Elin;Havulinna, Aki S.;Ho, Weang K.;Hopewell, Jemma C.;Eriksson, Niclas;Kleber, Marcus E.;Kristiansson, Kati;Lundmark, Per;Lyytikainen, Leo-Pekka;Rafelt, Suzanne;Shungin, Dmitry;Strawbridge, Rona J.;Thorleifsson, Gudmar;Tikkanen, Emmi;Van Zuydam, Natalie;Voight, Benjamin F.;Waite, Lindsay L.;Zhang, Weihua;Ziegler, Andreas;Absher, Devin;Altshuler, David;Balmforth, Anthony J.;Barroso, Ines;Braund, Peter S.;Burgdorf, Christof;Claudi-Boehm, Simone;Cox, David;Dimitriou, Maria;Do, Ron;Doney, Alex S. F.;El Mokhtari, NourEddine;Eriksson, Per;Fischer, Krista;Fontanillas, Pierre;Franco-Cereceda, Anders;Gigante, Bruna;Groop, Leif;Gustafsson, Stefan;Hager, Joerg;Hallmans, Goran;Han, Bok-Ghee;Hunt, Sarah E.;Kang, Hyun M.;Illig, Thomas;Kessler, Thorsten;Knowles, Joshua W.;Kolovou, Genovefa;Kuusisto, Johanna;Langenberg, Claudia;Langford, Cordelia;Leander, Karin;Lokki, Marja-Liisa;Lundmark, Anders;McCarthy, Mark I.;Meisinger, Christa;Melander, Olle;Mihailov, Evelin;Maouche, Seraya;Morris, Andrew D.;Mueller-Nurasyid, Martina;Nikus, Kjell;Peden, John F.;Rayner, N. William;Rasheed, Asif;Rosinger, Silke;Rubin, Diana;Rumpf, Moritz P.;Schaefer, Arne;Sivananthan, Mohan;Song, Ci;Stewart, Alexandre F. R.;Tan, Sian-Tsung;Thorgeirsson, Gudmundur;van der Schoot, C. Ellen;Wagner, Peter J.;Wells, George A.;Wild, Philipp S.;Yang, Tsun-Po;Amouyel, Philippe;Arveiler, Dominique;Basart, Hanneke;Boehnke, Michael;Boerwinkle, Eric;Brambilla, Paolo;Cambien, Francois;Cupples, Adrienne L.;de Faire, Ulf;Dehghan, Abbas;Diemert, Patrick;Epstein, Stephen E.;Evans, Alun;Ferrario, Marco M.;Ferrieres, Jean;Gauguier, Dominique;Go, Alan S.;Goodall, Alison H.;Gudnason, Villi;Hazen, Stanley L.;Holm, Hilma;Iribarren, Carlos;Jang, Yangsoo;Kahonen, Mika;Kee, Frank;Kim, Hyo-Soo;Klopp, Norman;Koenig, Wolfgang;Kratzer, Wolfgang;Kuulasmaa, Kari;Laakso, Markku;Laaksonen, Reijo;Lee, Ji-Young;Lind, Lars;Ouwehand, Willem H.;Parish, Sarah;Park, Jeong E.;Pedersen, Nancy L.;Peters, Annette;Quertermous, Thomas;Rader, Daniel J.;Salomaa, Veikko;Schadt, Eric;Shah, Svati H.;Sinisalo, Juha;Stark, Klaus;Stefansson, Kari;Tregouet, David-Alexandre;Virtamo, Jarmo;Wallentin, Lars;Wareham, Nicholas;Zimmermann, Martina E.;Nieminen, Markku S.;Hengstenberg, Christian;Sandhu, Manjinder S.;Pastinen, Tomi;Syvanen, Ann-Christine;Hovingh, G. Kees;Dedoussis, George;Franks, Paul W.;Lehtimaki, Terho;Metspalu, Andres;Zalloua, Pierre A.;Siegbahn, Agneta;Schreiber, Stefan;Ripatti, Samuli;Blankenberg, Stefan S.;Perola, Markus;Clarke, Robert;Boehm, Bernhard O.;O'Donnell, Christopher;Reilly, Muredach P.;Maerz, Winfried;Collins, Rory;Kathiresan, Sekar;Hamsten, Anders;Kooner, Jaspal S.;Thorsteinsdottir, Unnur;Danesh, John;Palmer, Colin N. A.;Roberts, Robert;Watkins, Hugh;Schunkert, Heribert;Samani, Nilesh J.
通讯作者：
Samani, Nilesh J.
DOI：
10.1056/nejmoa1012848
发表时间：
2012-01-26
期刊：
The New England journal of medicine
影响因子：
--
作者：
Berry JD;Dyer A;Cai X;Garside DB;Ning H;Thomas A;Greenland P;Van Horn L;Tracy RP;Lloyd-Jones DM
通讯作者：
Lloyd-Jones DM
影响因子：
64.8
作者：
Locke, Adam E.;Kahali, Bratati;Berndt, Sonja I.;Justice, Anne E.;Pers, Tune H.;Day, Felix R.;Powell, Corey;Vedantam, Sailaja;Buchkovich, Martin L.;Yang, Jian;Croteau-Chonka, Damien C.;Esko, Tonu;Fall, Tove;Ferreira, Teresa;Gustafsson, Stefan;Kutalik, Zoltan;Luan, Jian'an;Maegi, Reedik;Randall, Joshua C.;Winkler, Thomas W.;Wood, Andrew R.;Workalemahu, Tsegaselassie;Faul, Jessica D.;Smith, Jennifer A.;Zhao, Jing Hua;Zhao, Wei;Chen, Jin;Fehrmann, Rudolf;Hedman, Asa K.;Karjalainen, Juha;Schmidt, Ellen M.;Absher, Devin;Amin, Najaf;Anderson, Denise;Beekman, Marian;Bolton, Jennifer L.;Bragg-Gresham, L.;Buyske, Steven;Demirkan, Ayse;Deng, Guohong;Ehret, Georg B.;Feenstra, Bjarke;Feitosa, Mary F.;Fischer, Krista;Goel, Anuj;Gong, Jian;Jackson, Anne U.;Kanoni, Stavroula;Kleber, Marcus E.;Kristiansson, Kati;Lim, Unhee;Lotay, Vaneet;Mangino, Massimo;Leach, Irene Mateo;Medina-Gomez, Carolina;Medland, Sarah E.;Nalls, Michael A.;Palmer, Cameron D.;Pasko, Dorota;Pechlivanis, Sonali;Peters, Marjolein J.;Prokopenko, Inga;Shungin, Dmitry;Stancakova, Alena;Strawbridge, Rona J.;Sung, Yun Ju;Tanaka, Toshiko;Teumer, Alexander;Trompet, Stella;van der Laan, Sander W.;van Settee, Jessica;Van Vliet-Ostaptchouk, Jana V.;Wang, Zhaoming;Yengo, Loic;Zhang, Weihua;Isaacs, Aaron;Albrecht, Eva;Arnlov, Johan;Arscott, Gillian M.;Attwood, Antony P.;Bandinelli, Stefania;Barrett, Amy;Bas, Isabelita N.;Bellis, Claire;Bennett, Amanda J.;Berne, Christian;Blagieva, Roza;Blueher, Matthias;Bohringer, Stefan;Bonnycastle, Lori L.;Boettcher, Yvonne;Boyd, Heather A.;Bruinenberg, Marcel;Caspersen, Ida H.;Chen, Yii-Der Ida;Clarke, Robert;Daw, E. Warwick;de Craen, Anton J. M.;Delgado, Graciela;Dimitriou, Maria;Doney, Alex S. F.;Eklund, Niina;Estrada, Karol;Eury, Elodie;Folkersen, Lasse;Fraser, Ross M.;Garcia, Melissa E.;Geller, Frank;Giedraitis, Vilmantas;Gigante, Bruna;Go, Alan S.;Golay, Alain;Goodall, Alison H.;Gordon, Scott D.;Gorski, Mathias;Grabe, Hans-Joergen;Grallert, Harald;Grammer, Tanja B.;Graessler, Jurgen;Gronberg, Henrik;Groves, Christopher J.;Gusto, Gaeelle;Haessler, Jeffrey;Hall, Per;Haller, Toomas;Hallmans, Goran;Hartman, Catharina A.;Hassinen, Maija;Hayward, Caroline;Heard-Costa, Nancy L.;Helmer, Qinta;Hengstenberg, Christian;Holmen, Oddgeir;Hottenga, Jouke-Jan;James, Alan L.;Jeff, Janina M.;Johansson, Asa;Jolley, Jennifer;Juliusdottir, Thorhildur;Kinnunen, Leena;Koenig, Wolfgang;Koskenvuo, Markku;Kratzer, Wolfgang;Laitinen, Jaana;Lamina, Claudia;Leander, Karin;Lee, Nanette R.;Lichtner, Peter;Lind, Lars;Lindstrom, Jaana;Lo, Ken Sin;Lobbens, Stephane;Lorbeer, Roberto;Lu, Yingchang;Mach, Francois;Magnusson, Patrik K. E.;Mahajan, Anubha;McArdle, Wendy L.;McLachlan, Stela;Menni, Cristina;Merger, Sigrun;Mihailov, Evelin;Milani, Lili;Moayyeri, Alireza;Monda, Keri L.;Morken, Mario A.;Mulas, Antonella;Mueller, Gabriele;Mueller-Nurasyid, Martina;Musk, Arthur W.;Nagaraja, Ramaiah;Noethen, Markus M.;Nolte, Ilja M.;Pilz, Stefan;Rayner, Nigel W.;Renstrom, Frida;Rettig, Rainer;Ried, Janina S.;Ripke, Stephan;Robertson, Neil R.;Rose, Lynda M.;Sanna, Serena;Scharnagl, Hubert;Scholtens, Salome;Schumacher, Fredrick R.;Scott, William R.;Seufferlein, Thomas;Shi, Jianxin;Smith, Albert Vernon;Smolonska, Joanna;Stanton, Alice V.;Steinthorsdottir, Valgerdur;Stirrups, Kathleen;Stringham, Heather M.;Sundstrom, Johan;Swertz, Morris A.;Swift, Amy J.;Syvanen, Ann-Christine;Tan, Sian-Tsung;Tayo, Bamidele O.;Thorand, Barbara;Thorleifsson, Gudmar;Tyrer, Jonathan P.;Uh, Hae-Won;Vandenput, Liesbeth;Verhulst, Frank C.;Vermeulen, Sita H.;Verweij, Niek;Vonk, Judith M.;Waite, Lindsay L.;Warren, Helen R.;Waterworth, Dawn;Weedon, Michael N.;Wilkens, Lynne R.;Willenborg, Christina;Wilsgaard, Tom;Wojczynski, Mary K.;Wong, Andrew;Wrightl, Alan F.;Zhang, Qunyuan;Brennan, Eoin P.;Choi, Murim;Dastani, Zari;Drong, Alexander W.;Eriksson, Per;Franco-Cereceda, Anders;Gadin, Jesper R.;Gharavi, Ali G.;Goddard, Michael E.;Handsaker, Robert E.;Huang, Jinyan;Karpe, Fredrik;Kathiresan, Sekar;Keildson, Sarah;Kiryluk, Krzysztof;Kubo, Michiaki;Lee, Jong-Young;Liang, Liming;Lifton, Richard P.;Ma, Baoshan;McCarroll, Steven A.;McKnight, Amy J.;Min, Josine L.;Moffatt, Miriam F.;Montgomery, Grant W.;Murabito, Joanne M.;Nicholson, George;Nyholt, Dale R.;Okada, Yukinori;Perry, John R. B.;Dorajoo, Rajkumar;Reinmaa, Eva;Salem, Rany M.;Sandholm, Niina;Scott, Robert A.;Stolk, Lisette;Takahashi, Atsushi;Tanaka, Toshihiro;van 't Hooft, Ferdinand M.;Vinkhuyzen, Anna A. E.;Westra, Harm-Jan;Zheng, Wei;Zondervan, Krina T.;Heath, Andrew C.;Arveiler, Dominique;Bakker, Stephan J. L.;Beilby, John;Bergman, Richard N.;Blangero, John;Bovet, Pascal;Campbell, Harry;Caulfield, Mark J.;Cesana, Giancarlo;Chakravarti, Aravinda;Chasman, Daniel I.;Chines, Peter S.;Collins, Francis S.;Crawford, Dana C.;Cupples, L. Adrienne;Cusi, Daniele;Danesh, John;de Faire, Ulf;den Ruijter, Hester M.;Dominiczak, Anna F.;Erbel, Raimund;Erdmann, Jeanette;Eriksson, Johan G.;Farrall, Martin;Felix, Stephan B.;Ferrannini, Ele;Ferrieres, Jean;Ford, Ian;Forouhi, Nita G.;Forrester, Terrence;Franco, Oscar H.;Gansevoort, Ron T.;Gejman, Pablo V.;Gieger, Christian;Gottesman, Omri;Gudnason, Vilmundur;Gyllensten, Ulf;Hall, Alistair S.;Harris, Tamara B.;Hattersley, Andrew T.;Hicks, Andrew A.;Hindorff, Lucia A.;Hingorani, Aroon D.;Hofman, Albert;Homuth, Georg;Hovingh, G. Kees;Humphries, Steve E.;Hunt, Steven C.;Hypponen, Elina;Illig, Thomas;Jacobs, Kevin B.;Jarvelin, Marjo-Riitta;Joeckel, Karl-Heinz;Johansen, Berit;Jousilahti, Pekka;Jukema, J. Wouter;Jula, Antti M.;Kaprio, Jaakko;Kastelein, John J. P.;Keinanen-Kiukaanniemi, Sirkka M.;Kiemeney, Lambertus A.;Knekt, Paul;Kooner, Jaspal S.;Kooperberg, Charles;Kovacs, Peter;Kraja, Aldi T.;Kumari, Meena;Kuusisto, Johanna;Lakka, Timo A.;Langenberg, Claudia;Le Marchand, Laic;Lehtimaki, Terho;Lyssenko, Valeriya;Mannisto, Satu;Marette, Andre;Matise, Tara C.;McKenzie, Colin A.;McKnight, Barbara;Moll, Frans L.;Morris, Andrew D.;Morris, Andrew P.;Murray, Jeffrey C.;Nelis, Mari;Ohlsson, Claes;Oldehinkel, Albertine J.;Ong, Ken K.;Madden, Pamela A. F.;Pasterkamp, Gerard;Peden, John F.;Peters, Annette;Postma, Dirkje S.;Pramstaller, Peter P.;Price, Jackie F.;Qi, Lu;Raitakari, Olli T.;Rankinen, Tuomo;Rao, D. C.;Rice, Treva K.;Ridker, Paul M.;Rioux, John D.;Ritchie, Marylyn D.;Rudan, Igor;Salomaa, Veikko;Samani, Nilesh J.;Saramines, Jouko;Sarzynski, Mark A.;Schunkert, Heribert;Schwarz, Peter E. H.;Sever, Peter;Shuldiner, Alan R.;Sinisalo, Juha;Stolk, Ronald P.;Strauch, Konstantin;Toenjes, Anke;Tregouet, David-Alexandre;Tremblay, Angelo;Tremoli, Elena;Virtamo, Jarmo;Vohl, Marie-Claude;Voelker, Uwe;Waeber, Gerard;Willemsen, Gonneke;Witteman, Jacqueline C.;Zillikens, M. Carola;Adair, Linda S.;Amouyel, Philippe;Asselbergs, Folkert W.;Assimes, Themistocles L.;Bochud, Murielle;Boehm, Bernhard O.;Boerwinkle, Eric;Bornstein, Stefan R.;Bottinger, Erwin P.;Bouchard, Claude;Cauchi, Stephane;Chambers, John C.;Chanock, Stephen J.;Cooper, Richard S.;de Bakker, Paul I. W.;Dedoussis, George;Ferrucci, Luigi;Franks, Paul W.;Froguel, Philippe;Groop, Leif C.;Haiman, Christopher A.;Hamsten, Anders;Hui, Jennie;Hunter, David J.;Hveem, Kristian;Kaplan, Robert C.;Kivimaki, Mika;Kuh, Diana;Laakso, Markku;Liu, Yongmei;Martin, Nicholas G.;Maerz, Winfried;Melbve, Mads;Metspalu, Andres;Moebus, Susanne;Munroe, Patricia B.;Njolstad, Inger;Oostra, Ben A.;Palmer, Colin N. A.;Pedersen, Nancy L.;Perola, Markus;Perusse, Louis;Peters, Ulrike;Power, Chris;Quertermous, Thomas;Rauramaa, Rainer;Rivadeneira, Fernando;Saaristo, Timo E.;Saleheen, Danish;Sattar, Naveed;Schadt, Eric E.;Schlessinger, David;Slagboom, P. Eline;Snieder, Harold;Spector, Tim D.;Thorsteinsdottir, Unnu R.;Stumvoll, Michael;Tuomilehto, Jaakko;Uitterlinden, Andre G.;Uusitupa, Matti;van der Harst, Pim;Walker, Mark;Wallaschofski, Henri;Wareham, Nicholas J.;Watkins, Hugh;Weir, David R.;Wichmann, H-Erich;Wilson, James F.;Zanen, Pieter;Borecki, Ingrid B.;Deloukas, Panos;Fox, Caroline S.;Heid, Iris M.;O'Connell, Jeffrey R.;Strachan, David P.;Stefansson, Kari;van Duijri, Cornelia M.;Abecasis, Goncalo R.;Franke, Lude;Frayling, Timothy M.;McCarthy, Mark I.;Visscher, Peter M.;Scherag, Andre;Willer, Cristen J.;Boehnke, Michael;Mohlke, Karen L.;Lindgren, Cecilia M.;Beckmann, Jacques S.;Barroso, Ines;North, Kari E.;Ingelsson, Erik;Hirschhorn, Joel N.;Loos, Ruth J. F.;Speliotes, Elizabeth K.
通讯作者：
Speliotes, Elizabeth K.