A Journey through Genetic Architecture and Predisposition of Coronary Artery Disease

Author(s): Robert Roberts*, Chih Chao Chang

Journal Name: Current Genomics

Volume 21 , Issue 5 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Introduction: To halt the spread of coronary artery disease (CAD), the number one killer in the world, requires primary prevention. Fifty percent of all Americans are expected to experience a cardiac event; the challenge is identifying those at risk. 40 to 60% of predisposition to CAD is genetic. The first genetic risk variant, 9p21, was discovered in 2007. Genome-Wide Association Studies has since discovered hundreds of genetic risk variants. The genetic burden for CAD can be expressed as a single number, Genetic Risk Score (GRS). Assessment of GRS to risk stratify for CAD was superior to conventional risk factors in several large clinical trials assessing statin therapy, and more recently in a population of nearly 500,000 (UK Biobank). Studies were performed based on prospective genetic risk stratification for CAD. These studies showed that a favorable lifestyle was associated with a 46% reduction in cardiac events and programmed exercise, a 50% reduction in cardiac events. Genetic risk score is superior to conventional risk factors, and is markedly attenuated by lifestyle changes and drug therapy. Genetic risk can be determined at birth or any time thereafter.

Conclusion: Utilizing the GRS to risk stratify young, asymptomatic individuals could provide a paradigm shift in the primary prevention of CAD and significantly halt its spread.

Keywords: Genome-wide association studies, coronary artery disease, genetic risk stratification, genetics, primary, prevention, genetic risk variants, genomic.

Lander, E.S.; Linton, L.M.; Birren, B.; Nusbaum, C.; Zody, M.C.; Baldwin, J.; Devon, K.; Dewar, K.; Doyle, M.; FitzHugh, W.; Funke, R.; Gage, D.; Harris, K.; Heaford, A.; Howland, J.; Kann, L.; Lehoczky, J.; LeVine, R.; McEwan, P.; McKernan, K.; Meldrim, J.; Mesirov, J.P.; Miranda, C.; Morris, W.; Naylor, J.; Raymond, C.; Rosetti, M.; Santos, R.; Sheridan, A.; Sougnez, C.; Stange-Thomann, Y.; Stojanovic, N.; Subramanian, A.; Wyman, D.; Rogers, J.; Sulston, J.; Ainscough, R.; Beck, S.; Bentley, D.; Burton, J.; Clee, C.; Carter, N.; Coulson, A.; Deadman, R.; Deloukas, P.; Dunham, A.; Dunham, I.; Durbin, R.; French, L.; Grafham, D.; Gregory, S.; Hubbard, T.; Humphray, S.; Hunt, A.; Jones, M.; Lloyd, C.; McMurray, A.; Matthews, L.; Mercer, S.; Milne, S.; Mullikin, J.C.; Mungall, A.; Plumb, R.; Ross, M.; Shownkeen, R.; Sims, S.; Waterston, R.H.; Wilson, R.K.; Hillier, L.W.; McPherson, J.D.; Marra, M.A.; Mardis, E.R.; Fulton, L.A.; Chinwalla, A.T.; Pepin, K.H.; Gish, W.R.; Chissoe, S.L.; Wendl, M.C.; Delehaunty, K.D.; Miner, T.L.; Delehaunty, A.; Kramer, J.B.; Cook, L.L.; Fulton, R.S.; Johnson, D.L.; Minx, P.J.; Clifton, S.W.; Hawkins, T.; Branscomb, E.; Predki, P.; Richardson, P.; Wenning, S.; Slezak, T.; Doggett, N.; Cheng, J.F.; Olsen, A.; Lucas, S.; Elkin, C.; Uberbacher, E.; Frazier, M.; Gibbs, R.A.; Muzny, D.M.; Scherer, S.E.; Bouck, J.B.; Sodergren, E.J.; Worley, K.C.; Rives, C.M.; Gorrell, J.H.; Metzker, M.L.; Naylor, S.L.; Kucherlapati, R.S.; Nelson, D.L.; Weinstock, G.M.; Sakaki, Y.; Fujiyama, A.; Hattori, M.; Yada, T.; Toyoda, A.; Itoh, T.; Kawagoe, C.; Watanabe, H.; Totoki, Y.; Taylor, T.; Weissenbach, J.; Heilig, R.; Saurin, W.; Artiguenave, F.; Brottier, P.; Bruls, T.; Pelletier, E.; Robert, C.; Wincker, P.; Smith, D.R.; Doucette-Stamm, L.; Rubenfield, M.; Weinstock, K.; Lee, H.M.; Dubois, J.; Rosenthal, A.; Platzer, M.; Nyakatura, G.; Taudien, S.; Rump, A.; Yang, H.; Yu, J.; Wang, J.; Huang, G.; Gu, J.; Hood, L.; Rowen, L.; Madan, A.; Qin, S.; Davis, R.W.; Federspiel, N.A.; Abola, A.P.; Proctor, M.J.; Myers, R.M.; Schmutz, J.; Dickson, M.; Grimwood, J.; Cox, D.R.; Olson, M.V.; Kaul, R.; Raymond, C.; Shimizu, N.; Kawasaki, K.; Minoshima, S.; Evans, G.A.; Athanasiou, M.; Schultz, R.; Roe, B.A.; Chen, F.; Pan, H.; Ramser, J.; Lehrach, H.; Reinhardt, R.; McCombie, W.R.; de la Bastide, M.; Dedhia, N.; Blöcker, H.; Hornischer, K.; Nordsiek, G.; Agarwala, R.; Aravind, L.; Bailey, J.A.; Bateman, A.; Batzoglou, S.; Birney, E.; Bork, P.; Brown, D.G.; Burge, C.B.; Cerutti, L.; Chen, H.C.; Church, D.; Clamp, M.; Copley, R.R.; Doerks, T.; Eddy, S.R.; Eichler, E.E.; Furey, T.S.; Galagan, J.; Gilbert, J.G.; Harmon, C.; Hayashizaki, Y.; Haussler, D.; Hermjakob, H.; Hokamp, K.; Jang, W.; Johnson, L.S.; Jones, T.A.; Kasif, S.; Kaspryzk, A.; Kennedy, S.; Kent, W.J.; Kitts, P.; Koonin, E.V.; Korf, I.; Kulp, D.; Lancet, D.; Lowe, T.M.; McLysaght, A.; Mikkelsen, T.; Moran, J.V.; Mulder, N.; Pollara, V.J.; Ponting, C.P.; Schuler, G.; Schultz, J.; Slater, G.; Smit, A.F.; Stupka, E.; Szustakowki, J.; Thierry-Mieg, D.; Thierry-Mieg, J.; Wagner, L.; Wallis, J.; Wheeler, R.; Williams, A.; Wolf, Y.I.; Wolfe, K.H.; Yang, S.P.; Yeh, R.F.; Collins, F.; Guyer, M.S.; Peterson, J.; Felsenfeld, A.; Wetterstrand, K.A.; Patrinos, A.; Morgan, M.J.; de Jong, P.; Catanese, J.J.; Osoegawa, K.; Shizuya, H.; Choi, S.; Chen, Y.J.; Szustakowki, J. International Human Genome Sequencing ConsortiumInitial sequencing and analysis of the human genome. Nature, 2001, 409(6822), 860-921.
[http://dx.doi.org/10.1038/35057062] [PMID: 11237011]
International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature, 2004, 431(7011), 931-945.
[http://dx.doi.org/10.1038/nature03001] [PMID: 15496913]
Wald, N.J.; Law, M.R. A strategy to reduce cardiovascular disease by more than 80%. BMJ, 2003, 326(7404), 1419. [published correction appears in BMJ. 2003 Sep 13;327(7415):586] [published correction appears in BMJ. 2006 Sep;60(9):823]
[http://dx.doi.org/10.1136/bmj.326.7404.1419] [PMID: 12829553]
Zdravkovic, S.; Wienke, A.; Pedersen, N.L.; Marenberg, M.E.; Yashin, A.I.; De Faire, U. Heritability of death from coronary heart disease: a 36-year follow-up of 20 966 Swedish twins. J. Intern. Med., 2002, 252(3), 247-254.
[http://dx.doi.org/10.1046/j.1365-2796.2002.01029.x] [PMID: 12270005]
Wienke, A.; Holm, N.V.; Skytthe, A.; Yashin, A.I. The heritability of mortality due to heart diseases: a correlated frailty model applied to Danish twins. Twin Res., 2001, 4(4), 266-274.
[http://dx.doi.org/10.1375/twin.4.4.266] [PMID: 11665307]
Marenberg, M.E.; Risch, N.; Berkman, L.F.; Floderus, B.; de Faire, U. Genetic susceptibility to death from coronary heart disease in a study of twins. N. Engl. J. Med., 1994, 330(15), 1041-1046.
[http://dx.doi.org/10.1056/NEJM199404143301503] [PMID: 8127331]
Chan, L.; Boerwinkle, E. Gene-environment interactions and gene therapy in atherosclerosis. Cardiology, 1994, 2, 130-137.
DiMasi, J.A.; Grabowski, H.G.; Hansen, R.W. The cost of drug development. N. Engl. J. Med., 2015, 372(20), 1972.
[http://dx.doi.org/10.1056/NEJMc1504317] [PMID: 25970070]
Roberts, R. Genetics of coronary artery disease. Circ. Res., 2014, 114(12), 1890-1903.
[http://dx.doi.org/10.1161/CIRCRESAHA.114.302692] [PMID: 24902973]
Daw, E.W.; Chen, S.N.; Czernuszewicz, G.; Lombardi, R.; Lu, Y.; Ma, J.; Roberts, R.; Shete, S.; Marian, A.J. Genome-wide mapping of modifier chromosomal loci for human hypertrophic cardiomyopathy. Hum. Mol. Genet., 2007, 16(20), 2463-2471.
[http://dx.doi.org/10.1093/hmg/ddm202] [PMID: 17652099]
Hejtmancik, J.F.; Brink, P.A.; Towbin, J.; Hill, R.; Brink, L.; Tapscott, T.; Trakhtenbroit, A.; Roberts, R. Localization of gene for familial hypertrophic cardiomyopathy to chromosome 14q1 in a diverse US population. Circulation, 1991, 83(5), 1592-1597.
[http://dx.doi.org/10.1161/01.CIR.83.5.1592] [PMID: 2022018]
Jarcho, J.A.; McKenna, W.; Pare, J.A.; Solomon, S.D.; Holcombe, R.F.; Dickie, S.; Levi, T.; Donis-Keller, H.; Seidman, J.G.; Seidman, C.E. Mapping a gene for familial hypertrophic cardiomyopathy to chromosome 14q1. N. Engl. J. Med., 1989, 321(20), 1372-1378.
[http://dx.doi.org/10.1056/NEJM198911163212005] [PMID: 2811944]
Geisterfer-Lowrance, A.A.; Kass, S.; Tanigawa, G.; Vosberg, H.P.; McKenna, W.; Seidman, C.E.; Seidman, J.G. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell, 1990, 62(5), 999-1006.
[http://dx.doi.org/10.1016/0092-8674(90)90274-I] [PMID: 1975517]
Geisterfer-Lowrance, A.A.T.; Christe, M.; Conner, D.A.; Ingwall, J.S.; Schoen, F.J.; Seidman, C.E.; Seidman, J.G. A mouse model of familial hypertrophic cardiomyopathy. Science, 1996, 272(5262), 731-734.
[http://dx.doi.org/10.1126/science.272.5262.731] [PMID: 8614836]
Marian, A.J.; Wu, Y.; Lim, D-S.; McCluggage, M.; Youker, K.; Yu, Q-T.; Brugada, R.; DeMayo, F.; Quinones, M.; Roberts, R. A transgenic rabbit model for human hypertrophic cardiomyopathy. J. Clin. Invest., 1999, 104(12), 1683-1692.
[http://dx.doi.org/10.1172/JCI7956] [PMID: 10606622]
Gollob, M.H.; Roberts, R. AMP-activated protein kinase and familial Wolff-Parkinson-White syndrome: new perspectives on heart development and arrhythmogenesis. Eur. Heart J., 2002, 23(9), 679-681.
[http://dx.doi.org/10.1053/euhj.2001.2954] [PMID: 11977988]
Sidhu, J.S.; Rajawat, Y.S.; Rami, T.G.; Gollob, M.H.; Wang, Z.; Yuan, R.; Marian, A.J.; DeMayo, F.J.; Weilbacher, D.; Taffet, G.E.; Davies, J.K.; Carling, D.; Khoury, D.S.; Roberts, R. Transgenic mouse model of ventricular preexcitation and atrioventricular reentrant tachycardia induced by an AMP-activated protein kinase loss-of-function mutation responsible for Wolff-Parkinson-White syndrome. Circulation, 2005, 111(1), 21-29.
[http://dx.doi.org/10.1161/01.CIR.0000151291.32974.D5] [PMID: 15611370]
Ahmad, F.; Li, D.; Karibe, A.; Gonzalez, O.; Tapscott, T.; Hill, R.; Weilbaecher, D.; Blackie, P.; Furey, M.; Gardner, M.; Bachinski, L.L.; Roberts, R. Localization of a gene responsible for arrhythmogenic right ventricular dysplasia to chromosome 3p23. Circulation, 1998, 98(25), 2791-2795.
[http://dx.doi.org/10.1161/01.CIR.98.25.2791] [PMID: 9860777]
Marian, A.J.; Brugada, R.; Roberts, R. chapter 55: mendelian basis of congenital and other cardiovascular disease. hurst’s. heart, 2015, 14e.
Ku, C.S.; Naidoo, N.; Pawitan, Y. Revisiting Mendelian disorders through exome sequencing. Hum. Genet., 2011, 129(4), 351-370.
[http://dx.doi.org/10.1007/s00439-011-0964-2] [PMID: 21331778]
Morgan, T.M.; Krumholz, H.M.; Lifton, R.P.; Spertus, J.A. Nonvalidation of reported genetic risk factors for acute coronary syndrome in a large-scale replication study. JAMA, 2007, 297(14), 1551-1561.
[http://dx.doi.org/10.1001/jama.297.14.1551] [PMID: 17426274]
Anand, S.S.; Xie, C.; Paré, G.; Montpetit, A.; Rangarajan, S.; McQueen, M.J.; Cordell, H.J.; Keavney, B.; Yusuf, S.; Hudson, T.J.; Engert, J.C. INTERHEART Investigators Genetic variants associated with myocardial infarction risk factors in over 8000 individuals from five ethnic groups: The INTERHEART Genetics Study. Circ Cardiovasc Genet, 2009, 2(1), 16-25.
[http://dx.doi.org/10.1161/CIRCGENETICS.108.813709] [PMID: 20031563]
Kruglyak, L.; Nickerson, D.A. Variation is the spice of life. Nat. Genet., 2001, 27(3), 234-236.
[http://dx.doi.org/10.1038/85776] [PMID: 11242096]
Kruglyak, L. Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nat. Genet., 1999, 22(2), 139-144.
[http://dx.doi.org/10.1038/9642] [PMID: 10369254]
Hirschhorn, J.N.; Daly, M.J. Genome-wide association studies for common diseases and complex traits. Nat. Rev. Genet., 2005, 6(2), 95-108.
[http://dx.doi.org/10.1038/nrg1521] [PMID: 15716906]
Wang, W.Y.; Barratt, B.J.; Clayton, D.G.; Todd, J.A. Genome-wide association studies: theoretical and practical concerns. Nat. Rev. Genet., 2005, 6(2), 109-118.
[http://dx.doi.org/10.1038/nrg1522] [PMID: 15716907]
Thomas, D.C.; Haile, R.W.; Duggan, D. Recent developments in genomewide association scans: a workshop summary and review. Am. J. Hum. Genet., 2005, 77(3), 337-345.
[http://dx.doi.org/10.1086/432962] [PMID: 16080110]
Dandona, S.; Stewart, A.F.R.; Roberts, R. Genomics in coronary artery disease: past, present and future. Can. J. Cardiol., 2010, 26(Suppl. A), 56A-59A.
[http://dx.doi.org/10.1016/S0828-282X(10)71064-3] [PMID: 20386763]
Roberts, R. A customized genetic approach to the number one killer: coronary artery disease. Curr. Opin. Cardiol., 2008, 23(6), 629-633.
[http://dx.doi.org/10.1097/HCO.0b013e32830e6b4e]] [PMID: 18830080]
Roberts, R. New gains in understanding coronary artery disease, Interview with Dr Robert Roberts. Affymetrix Microarray Bull., 2007, 3(2), 1-4.
Altshuler, D.; Donnelly, P. International HapMap Consortium. A haplotype map of the human genome. Nature, 2005, 437(7063), 1299-1320.
[http://dx.doi.org/10.1038/nature04226] [PMID: 16255080]
Gibbs, R.; Belmont, J.; Hardenbol, P. International HapMap Consortium. The International HapMap Project. Nature, 2003, 426(6968), 789-796.
[http://dx.doi.org/10.1038/nature02168] [PMID: 14685227]
Auton, A.; Brooks, L.D.; Durbin, R.M.; Garrison, E.P.; Kang, H.M.; Korbel, J.O.; Marchini, J.L.; McCarthy, S.; McVean, G.A.; Abecasis, G.R. 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature, 2015, 526(7571), 68-74.
[http://dx.doi.org/10.1038/nature15393] [PMID: 26432245]
Kannel, W.B.; Dawber, T.R.; Kagan, A.; Revotskie, N.; Stokes, J., III Factors of risk in the development of coronary heart disease--six year follow-up experience. The Framingham Study. Ann. Intern. Med., 1961, 55(1), 33-50.
[http://dx.doi.org/10.7326/0003-4819-55-1-33] [PMID: 13751193]
Yusuf, S.; Hawken, S.; Ounpuu, S. Dans, T.; Avezum, A.; Lanas, F.; McQueen, M.; Budaj, A.; Pais, P.; Varigos, J.; Lisheng, L. INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet, 2004, 364(9438), 937-952.
[http://dx.doi.org/10.1016/S0140-6736(04)17018-9] [PMID: 15364185]
Yusuf, S.; Bosch, J.; Dagenais, G.; Zhu, J.; Xavier, D.; Liu, L.; Pais, P.; López-Jaramillo, P.; Leiter, L.A. Dans, A.; Avezum, A.; Piegas, L.S.; Parkhomenko, A.; Keltai, K.; Keltai, M.; Sliwa, K.; Peters, R.J.; Held, C.; Chazova, I.; Yusoff, K.; Lewis, B.S.; Jansky, P.; Khunti, K.; Toff, W.D.; Reid, C.M.; Varigos, J.; Sanchez-Vallejo, G.; McKelvie, R.; Pogue, J.; Jung, H.; Gao, P.; Diaz, R.; Lonn, E. HOPE-3 Investigators. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N. Engl. J. Med., 2016, 374(21), 2021-2031.
[http://dx.doi.org/10.1056/NEJMoa1600176] [PMID: 27040132]
Murray, C.J.; Lopez, A.D. Measuring the global burden of disease. N. Engl. J. Med., 2013, 369(5), 448-457.
[http://dx.doi.org/10.1056/NEJMra1201534] [PMID: 23902484]
Navar-Boggan, A.M.; Peterson, E.D.; D’Agostino, R.B.S., Sr; Neely, B.; Sniderman, A.D.; Pencina, M.J. Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease. Circulation, 2015, 131(5), 451-458.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.012477] [PMID: 25623155]
Chaisson, M.J.P.; Sanders, A.D.; Zhao, X.; Malhotra, A.; Porubsky, D.; Rausch, T.; Gardner, E.J.; Rodriguez, O.L.; Guo, L.; Collins, R.L.; Fan, X.; Wen, J.; Handsaker, R.E.; Fairley, S.; Kronenberg, Z.N.; Kong, X.; Hormozdiari, F.; Lee, D.; Wenger, A.M.; Hastie, A.R.; Antaki, D.; Anantharaman, T.; Audano, P.A.; Brand, H.; Cantsilieris, S.; Cao, H.; Cerveira, E.; Chen, C.; Chen, X.; Chin, C.S.; Chong, Z.; Chuang, N.T.; Lambert, C.C.; Church, D.M.; Clarke, L.; Farrell, A.; Flores, J.; Galeev, T.; Gorkin, D.U.; Gujral, M.; Guryev, V.; Heaton, W.H.; Korlach, J.; Kumar, S.; Kwon, J.Y.; Lam, E.T.; Lee, J.E.; Lee, J.; Lee, W.P.; Lee, S.P.; Li, S.; Marks, P.; Viaud-Martinez, K.; Meiers, S.; Munson, K.M.; Navarro, F.C.P.; Nelson, B.J.; Nodzak, C.; Noor, A.; Kyriazopoulou-Panagiotopoulou, S.; Pang, A.W.C.; Qiu, Y.; Rosanio, G.; Ryan, M.; Stütz, A.; Spierings, D.C.J.; Ward, A.; Welch, A.E.; Xiao, M.; Xu, W.; Zhang, C.; Zhu, Q.; Zheng-Bradley, X.; Lowy, E.; Yakneen, S.; McCarroll, S.; Jun, G.; Ding, L.; Koh, C.L.; Ren, B.; Flicek, P.; Chen, K.; Gerstein, M.B.; Kwok, P.Y.; Lansdorp, P.M.; Marth, G.T.; Sebat, J.; Shi, X.; Bashir, A.; Ye, K.; Devine, S.E.; Talkowski, M.E.; Mills, R.E.; Marschall, T.; Korbel, J.O.; Eichler, E.E.; Lee, C. Multi-platform discovery of haplotype-resolved structural variation in human genomes. Nat. Commun., 2019, 10(1), 1784.
[http://dx.doi.org/10.1038/s41467-018-08148-z] [PMID: 30992455]
Sudmant, P.H.; Rausch, T.; Gardner, E.J.; Handsaker, R.E.; Abyzov, A.; Huddleston, J.; Zhang, Y.; Ye, K.; Jun, G.; Fritz, M.H.; Konkel, M.K.; Malhotra, A.; Stütz, A.M.; Shi, X.; Casale, F.P.; Chen, J.; Hormozdiari, F.; Dayama, G.; Chen, K.; Malig, M.; Chaisson, M.J.P.; Walter, K.; Meiers, S.; Kashin, S.; Garrison, E.; Auton, A.; Lam, H.Y.K.; Mu, X.J.; Alkan, C.; Antaki, D.; Bae, T.; Cerveira, E.; Chines, P.; Chong, Z.; Clarke, L.; Dal, E.; Ding, L.; Emery, S.; Fan, X.; Gujral, M.; Kahveci, F.; Kidd, J.M.; Kong, Y.; Lameijer, E.W.; McCarthy, S.; Flicek, P.; Gibbs, R.A.; Marth, G.; Mason, C.E.; Menelaou, A.; Muzny, D.M.; Nelson, B.J.; Noor, A.; Parrish, N.F.; Pendleton, M.; Quitadamo, A.; Raeder, B.; Schadt, E.E.; Romanovitch, M.; Schlattl, A.; Sebra, R.; Shabalin, A.A.; Untergasser, A.; Walker, J.A.; Wang, M.; Yu, F.; Zhang, C.; Zhang, J.; Zheng-Bradley, X.; Zhou, W.; Zichner, T.; Sebat, J.; Batzer, M.A.; McCarroll, S.A.; Mills, R.E.; Gerstein, M.B.; Bashir, A.; Stegle, O.; Devine, S.E.; Lee, C.; Eichler, E.E.; Korbel, J.O. 1000 Genomes Project Consortium. An integrated map of structural variation in 2,504 human genomes. Nature, 2015, 526(7571), 75-81.
[http://dx.doi.org/10.1038/nature15394] [PMID: 26432246]
Chaisson, M.J.P.; Wilson, R.K.; Eichler, E.E. Genetic variation and the de novo assembly of human genomes. Nat. Rev. Genet., 2015, 16(11), 627-640.
[http://dx.doi.org/10.1038/nrg3933] [PMID: 26442640]
Eichler, E.E. Genetic variation, comparative genomics, and the diagnosis of disease. N. Engl. J. Med., 2019, 381(1), 64-74.
[http://dx.doi.org/10.1056/NEJMra1809315] [PMID: 31269367]
Bhangale, T.R.; Rieder, M.J.; Livingston, R.J.; Nickerson, D.A. Comprehensive identification and characterization of diallelic insertion-deletion polymorphisms in 330 human candidate genes. Hum. Mol. Genet., 2005, 14(1), 59-69.
[http://dx.doi.org/10.1093/hmg/ddi006] [PMID: 15525656]
Carlson, C. Considerations for SNP selection. Genetic Variation: A Laboratory Manual; Winer, M.P., Ed.; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, 2007, pp. 263-281.
Sun, J.X.; Helgason, A.; Masson, G.; Ebenesersdóttir, S.S.; Li, H.; Mallick, S.; Gnerre, S.; Patterson, N.; Kong, A.; Reich, D.; Stefansson, K. A direct characterization of human mutation based on microsatellites. Nat. Genet., 2012, 44(10), 1161-1165.
[http://dx.doi.org/10.1038/ng.2398] [PMID: 22922873]
Hirakawa, M.; Tanaka, T.; Hashimoto, Y.; Kuroda, M.; Takagi, T.; Nakamura, Y. JSNP: a database of common gene variations in the Japanese population. Nucleic Acids Res., 2002, 30(1), 158-162.
[http://dx.doi.org/10.1093/nar/30.1.158] [PMID: 11752280]
Haga, H.; Yamada, R.; Ohnishi, Y.; Nakamura, Y.; Tanaka, T. Gene-based SNP discovery as part of the Japanese Millennium Genome Project: identification of 190,562 genetic variations in the human genome. Single-nucleotide polymorphism. J. Hum. Genet., 2002, 47(11), 605-610.
[http://dx.doi.org/10.1007/s100380200092] [PMID: 12436197]
Frazer, K.A.; Ballinger, D.G.; Cox, D.R.; Hinds, D.A.; Stuve, L.L.; Gibbs, R.A.; Belmont, J.W.; Boudreau, A.; Hardenbol, P.; Leal, S.M.; Pasternak, S.; Wheeler, D.A.; Willis, T.D.; Yu, F.; Yang, H.; Zeng, C.; Gao, Y.; Hu, H.; Hu, W.; Li, C.; Lin, W.; Liu, S.; Pan, H.; Tang, X.; Wang, J.; Wang, W.; Yu, J.; Zhang, B.; Zhang, Q.; Zhao, H.; Zhao, H.; Zhou, J.; Gabriel, S.B.; Barry, R.; Blumenstiel, B.; Camargo, A.; Defelice, M.; Faggart, M.; Goyette, M.; Gupta, S.; Moore, J.; Nguyen, H.; Onofrio, R.C.; Parkin, M.; Roy, J.; Stahl, E.; Winchester, E.; Ziaugra, L.; Altshuler, D.; Shen, Y.; Yao, Z.; Huang, W.; Chu, X.; He, Y.; Jin, L.; Liu, Y.; Shen, Y.; Sun, W.; Wang, H.; Wang, Y.; Wang, Y.; Xiong, X.; Xu, L.; Waye, M.M.; Tsui, S.K.; Xue, H.; Wong, J.T.; Galver, L.M.; Fan, J.B.; Gunderson, K.; Murray, S.S.; Oliphant, A.R.; Chee, M.S.; Montpetit, A.; Chagnon, F.; Ferretti, V.; Leboeuf, M.; Olivier, J.F.; Phillips, M.S.; Roumy, S.; Sallée, C.; Verner, A.; Hudson, T.J.; Kwok, P.Y.; Cai, D.; Koboldt, D.C.; Miller, R.D.; Pawlikowska, L.; Taillon-Miller, P.; Xiao, M.; Tsui, L.C.; Mak, W.; Song, Y.Q.; Tam, P.K.; Nakamura, Y.; Kawaguchi, T.; Kitamoto, T.; Morizono, T.; Nagashima, A.; Ohnishi, Y.; Sekine, A.; Tanaka, T.; Tsunoda, T.; Deloukas, P.; Bird, C.P.; Delgado, M.; Dermitzakis, E.T.; Gwilliam, R.; Hunt, S.; Morrison, J.; Powell, D.; Stranger, B.E.; Whittaker, P.; Bentley, D.R.; Daly, M.J.; de Bakker, P.I.; Barrett, J.; Chretien, Y.R.; Maller, J.; McCarroll, S.; Patterson, N.; Pe’er, I.; Price, A.; Purcell, S.; Richter, D.J.; Sabeti, P.; Saxena, R.; Schaffner, S.F.; Sham, P.C.; Varilly, P.; Altshuler, D.; Stein, L.D.; Krishnan, L.; Smith, A.V.; Tello-Ruiz, M.K.; Thorisson, G.A.; Chakravarti, A.; Chen, P.E.; Cutler, D.J.; Kashuk, C.S.; Lin, S.; Abecasis, G.R.; Guan, W.; Li, Y.; Munro, H.M.; Qin, Z.S.; Thomas, D.J.; McVean, G.; Auton, A.; Bottolo, L.; Cardin, N.; Eyheramendy, S.; Freeman, C.; Marchini, J.; Myers, S.; Spencer, C.; Stephens, M.; Donnelly, P.; Cardon, L.R.; Clarke, G.; Evans, D.M.; Morris, A.P.; Weir, B.S.; Tsunoda, T.; Mullikin, J.C.; Sherry, S.T.; Feolo, M.; Skol, A.; Zhang, H.; Zeng, C.; Zhao, H.; Matsuda, I.; Fukushima, Y.; Macer, D.R.; Suda, E.; Rotimi, C.N.; Adebamowo, C.A.; Ajayi, I.; Aniagwu, T.; Marshall, P.A.; Nkwodimmah, C.; Royal, C.D.; Leppert, M.F.; Dixon, M.; Peiffer, A.; Qiu, R.; Kent, A.; Kato, K.; Niikawa, N.; Adewole, I.F.; Knoppers, B.M.; Foster, M.W.; Clayton, E.W.; Watkin, J.; Gibbs, R.A.; Belmont, J.W.; Muzny, D.; Nazareth, L.; Sodergren, E.; Weinstock, G.M.; Wheeler, D.A.; Yakub, I.; Gabriel, S.B.; Onofrio, R.C.; Richter, D.J.; Ziaugra, L.; Birren, B.W.; Daly, M.J.; Altshuler, D.; Wilson, R.K.; Fulton, L.L.; Rogers, J.; Burton, J.; Carter, N.P.; Clee, C.M.; Griffiths, M.; Jones, M.C.; McLay, K.; Plumb, R.W.; Ross, M.T.; Sims, S.K.; Willey, D.L.; Chen, Z.; Han, H.; Kang, L.; Godbout, M.; Wallenburg, J.C.; L’Archevêque, P.; Bellemare, G.; Saeki, K.; Wang, H.; An, D.; Fu, H.; Li, Q.; Wang, Z.; Wang, R.; Holden, A.L.; Brooks, L.D.; McEwen, J.E.; Guyer, M.S.; Wang, V.O.; Peterson, J.L.; Shi, M.; Spiegel, J.; Sung, L.M.; Zacharia, L.F.; Collins, F.S.; Kennedy, K.; Jamieson, R.; Stewart, J. International HapMap Consortium. A second generation human haplotype map of over 3.1 million SNPs. Nature, 2007, 449(7164), 851-861.
[http://dx.doi.org/10.1038/nature06258] [PMID: 17943122]
McPherson, R.; Pertsemlidis, A.; Kavaslar, N.; Stewart, A.; Roberts, R.; Cox, D.R.; Hinds, D.A.; Pennacchio, L.A.; Tybjaerg-Hansen, A.; Folsom, A.R.; Boerwinkle, E.; Hobbs, H.H.; Cohen, J.C. A common allele on chromosome 9 associated with coronary heart disease. Science, 2007, 316(5830), 1488-1491.
[http://dx.doi.org/10.1126/science.1142447] [PMID: 17478681]
Helgadottir, A.; Thorleifsson, G.; Manolescu, A.; Gretarsdottir, S.; Blondal, T.; Jonasdottir, A.; Jonasdottir, A.; Sigurdsson, A.; Baker, A.; Palsson, A.; Masson, G.; Gudbjartsson, D.F.; Magnusson, K.P.; Andersen, K.; Levey, A.I.; Backman, V.M.; Matthiasdottir, S.; Jonsdottir, T.; Palsson, S.; Einarsdottir, H.; Gunnarsdottir, S.; Gylfason, A.; Vaccarino, V.; Hooper, W.C.; Reilly, M.P.; Granger, C.B.; Austin, H.; Rader, D.J.; Shah, S.H.; Quyyumi, A.A.; Gulcher, J.R.; Thorgeirsson, G.; Thorsteinsdottir, U.; Kong, A.; Stefansson, K. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science, 2007, 316(5830), 1491-1493.
[http://dx.doi.org/10.1126/science.1142842] [PMID: 17478679]
Wellcome Trust Case Control Consortium Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 2007, 447(7145), 661-678.
[http://dx.doi.org/10.1038/nature05911] [PMID: 17554300]
Saxena, R.; Voight, B.F.; Lyssenko, V.; Burtt, N.P.; de Bakker, P.I.; Chen, H.; Roix, J.J.; Kathiresan, S.; Hirschhorn, J.N.; Daly, M.J.; Hughes, T.E.; Groop, L.; Altshuler, D.; Almgren, P.; Florez, J.C.; Meyer, J.; Ardlie, K.; Bengtsson Boström, K.; Isomaa, B.; Lettre, G.; Lindblad, U.; Lyon, H.N.; Melander, O.; Newton-Cheh, C.; Nilsson, P.; Orho-Melander, M.; Råstam, L.; Speliotes, E.K.; Taskinen, M.R.; Tuomi, T.; Guiducci, C.; Berglund, A.; Carlson, J.; Gianniny, L.; Hackett, R.; Hall, L.; Holmkvist, J.; Laurila, E.; Sjögren, M.; Sterner, M.; Surti, A.; Svensson, M.; Svensson, M.; Tewhey, R.; Blumenstiel, B.; Parkin, M.; Defelice, M.; Barry, R.; Brodeur, W.; Camarata, J.; Chia, N.; Fava, M.; Gibbons, J.; Handsaker, B.; Healy, C.; Nguyen, K.; Gates, C.; Sougnez, C.; Gage, D.; Nizzari, M.; Gabriel, S.B.; Chirn, G.W.; Ma, Q.; Parikh, H.; Richardson, D.; Ricke, D.; Purcell, S. Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science, 2007, 316(5829), 1331-1336.
[http://dx.doi.org/10.1126/science.1142358] [PMID: 17463246]
Broadbent, H.M.; Peden, J.F.; Lorkowski, S.; Goel, A.; Ongen, H.; Green, F.; Clarke, R.; Collins, R.; Franzosi, M.G.; Tognoni, G.; Seedorf, U.; Rust, S.; Eriksson, P.; Hamsten, A.; Farrall, M.; Watkins, H. PROCARDIS consortium Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked SNPs in the ANRIL locus on chromosome 9p. Hum. Mol. Genet., 2008, 17(6), 806-814.
[http://dx.doi.org/10.1093/hmg/ddm352] [PMID: 18048406]
Ding, H.; Xu, Y.; Wang, X.; Wang, Q.; Zhang, L.; Tu, Y.; Yan, J.; Wang, W.; Hui, R.; Wang, C.Y.; Wang, D.W. 9p21 is a shared susceptibility locus strongly for coronary artery disease and weakly for ischemic stroke in Chinese Han population. Circ Cardiovasc Genet, 2009, 2(4), 338-346.
[http://dx.doi.org/10.1161/CIRCGENETICS.108.810226] [PMID: 20031605]
Zhou, L.; Zhang, X.; He, M.; Cheng, L.; Chen, Y.; Hu, F.B.; Wu, T. Associations between single nucleotide polymorphisms on chromosome 9p21 and risk of coronary heart disease in Chinese Han population. Arterioscler. Thromb. Vasc. Biol., 2008, 28(11), 2085-2089.
[http://dx.doi.org/10.1161/ATVBAHA.108.176065] [PMID: 18757290]
Shen, GQ; Li, L; Rao, S; Abdullah, KG; Ban, JM; Lee, B.S. Four SNPs on chromosome 9p21 in a South Korean population implicate a genetic locus that confers high cross-race risk for development of coronary artery disease. Arterioscler. Thromb. Vasc. Biol., 2008, 28(2), 360-365.
[PMID: 18048766]
Hinohara, K.; Nakajima, T.; Takahashi, M.; Hohda, S.; Sasaoka, T.; Nakahara, K.I.; Chida, K.; Sawabe, M.; Arimura, T.; Sato, A.; Lee, B.S.; Ban, J.M.; Yasunami, M.; Park, J.E.; Izumi, T.; Kimura, A. Replication of the association between a chromosome 9p21 polymorphism and coronary artery disease in Japanese and Korean populations. J. Hum. Genet., 2008, 53(4), 357-359.
[http://dx.doi.org/10.1007/s10038-008-0248-4] [PMID: 18264662]
Shen, G.Q.; Rao, S.; Martinelli, N.; Li, L.; Olivieri, O.; Corrocher, R.; Abdullah, K.G.; Hazen, S.L.; Smith, J.; Barnard, J.; Plow, E.F.; Girelli, D.; Wang, Q.K. Association between four SNPs on chromosome 9p21 and myocardial infarction is replicated in an Italian population. J. Hum. Genet., 2008, 53(2), 144-150.
[http://dx.doi.org/10.1007/s10038-007-0230-6] [PMID: 18066490]
Assimes, T.L.; Knowles, J.W.; Basu, A.; Iribarren, C.; Southwick, A.; Tang, H.; Absher, D.; Li, J.; Fair, J.M.; Rubin, G.D.; Sidney, S.; Fortmann, S.P.; Go, A.S.; Hlatky, M.A.; Myers, R.M.; Risch, N.; Quertermous, T. Susceptibility locus for clinical and subclinical coronary artery disease at chromosome 9p21 in the multi-ethnic ADVANCE study. Hum. Mol. Genet., 2008, 17(15), 2320-2328.
[http://dx.doi.org/10.1093/hmg/ddn132] [PMID: 18443000]
Coronary Artery Disease (C4D) Genetics Consortium. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat. Genet., 2011, 43(4), 339-344.
[http://dx.doi.org/10.1038/ng.782] [PMID: 21378988]
Preuss, M.; König, I.R.; Thompson, J.R.; Erdmann, J.; Absher, D.; Assimes, T.L.; Blankenberg, S.; Boerwinkle, E.; Chen, L.; Cupples, L.A.; Hall, A.S.; Halperin, E.; Hengstenberg, C.; Holm, H.; Laaksonen, R.; Li, M.; März, W.; McPherson, R.; Musunuru, K.; Nelson, C.P.; Burnett, M.S.; Epstein, S.E.; O’Donnell, C.J.; Quertermous, T.; Rader, D.J.; Roberts, R.; Schillert, A.; Stefansson, K.; Stewart, A.F.; Thorleifsson, G.; Voight, B.F.; Wells, G.A.; Ziegler, A.; Kathiresan, S.; Reilly, M.P.; Samani, N.J.; Schunkert, H. CARDIoGRAM Consortium CARDIoGRAM Consortium. Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study: a genome-wide association meta-analysis involving more than 22 000 cases and 60 000 controls. Circ Cardiovasc Genet, 2010, 3(5), 475-483.
[http://dx.doi.org/10.1161/CIRCGENETICS.109.899443] [PMID: 20923989]
Samani, N.J.; Erdmann, J.; Hall, A.S.; Hengstenberg, C.; Mangino, M.; Mayer, B.; Dixon, R.J.; Meitinger, T.; Braund, P.; Wichmann, H.E.; Barrett, J.H.; König, I.R.; Stevens, S.E.; Szymczak, S.; Tregouet, D.A.; Iles, M.M.; Pahlke, F.; Pollard, H.; Lieb, W.; Cambien, F.; Fischer, M.; Ouwehand, W.; Blankenberg, S.; Balmforth, A.J.; Baessler, A.; Ball, S.G.; Strom, T.M.; Braenne, I.; Gieger, C.; Deloukas, P.; Tobin, M.D.; Ziegler, A.; Thompson, J.R.; Schunkert, H. WTCCC and the Cardiogenics Consortium Genomewide association analysis of coronary artery disease. N. Engl. J. Med., 2007, 357(5), 443-453.
[http://dx.doi.org/10.1056/NEJMoa072366] [PMID: 17634449]
Howson, J.M.M.; Zhao, W.; Barnes, D.R.; Ho, W.K.; Young, R.; Paul, D.S.; Waite, L.L.; Freitag, D.F.; Fauman, E.B.; Salfati, E.L.; Sun, B.B.; Eicher, J.D.; Johnson, A.D.; Sheu, W.H.H.; Nielsen, S.F.; Lin, W.Y.; Surendran, P.; Malarstig, A.; Wilk, J.B.; Tybjærg-Hansen, A.; Rasmussen, K.L.; Kamstrup, P.R.; Deloukas, P.; Erdmann, J.; Kathiresan, S.; Samani, N.J.; Schunkert, H.; Watkins, H.; Do, R.; Rader, D.J.; Johnson, J.A.; Hazen, S.L.; Quyyumi, A.A.; Spertus, J.A.; Pepine, C.J.; Franceschini, N.; Justice, A.; Reiner, A.P.; Buyske, S.; Hindorff, L.A.; Carty, C.L.; North, K.E.; Kooperberg, C.; Boerwinkle, E.; Young, K.; Graff, M.; Peters, U.; Absher, D.; Hsiung, C.A.; Lee, W.J.; Taylor, K.D.; Chen, Y.H.; Lee, I.T.; Guo, X.; Chung, R.H.; Hung, Y.J.; Rotter, J.I.; Juang, J.J.; Quertermous, T.; Wang, T.D.; Rasheed, A.; Frossard, P.; Alam, D.S.; Majumder, A.A.S.; Di Angelantonio, E.; Chowdhury, R.; Chen, Y.I.; Nordestgaard, B.G.; Assimes, T.L.; Danesh, J.; Butterworth, A.S.; Saleheen, D. CARDIoGRAMplusC4D; EPIC-CVD. Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms. Nat. Genet., 2017, 49(7), 1113-1119.
[http://dx.doi.org/10.1038/ng.3874] [PMID: 28530674]
Schunkert, H.; König, IR; Kathiresan, S Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease Nat Genet, 2011, 43(4), 333-338.
van der Harst, P.; Verweij, N. Identification of 64 novel genetic loci provides an expanded view on the genetic architecture of coronary artery disease. Circ. Res., 2018, 122(3), 433-443.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.312086] [PMID: 29212778]
Nelson, C.P.; Goel, A.; Butterworth, A.S.; Kanoni, S.; Webb, T.R.; Marouli, E.; Zeng, L.; Ntalla, I.; Lai, F.Y.; Hopewell, J.C.; Giannakopoulou, O.; Jiang, T.; Hamby, S.E.; Di Angelantonio, E.; Assimes, T.L.; Bottinger, E.P.; Chambers, J.C.; Clarke, R.; Palmer, C.N.A.; Cubbon, R.M.; Ellinor, P.; Ermel, R.; Evangelou, E.; Franks, P.W.; Grace, C.; Gu, D.; Hingorani, A.D.; Howson, J.M.M.; Ingelsson, E.; Kastrati, A.; Kessler, T.; Kyriakou, T.; Lehtimäki, T.; Lu, X.; Lu, Y.; März, W.; McPherson, R.; Metspalu, A.; Pujades-Rodriguez, M.; Ruusalepp, A.; Schadt, E.E.; Schmidt, A.F.; Sweeting, M.J.; Zalloua, P.A.; AlGhalayini, K.; Keavney, B.D.; Kooner, J.S.; Loos, R.J.F.; Patel, R.S.; Rutter, M.K.; Tomaszewski, M.; Tzoulaki, I.; Zeggini, E.; Erdmann, J.; Dedoussis, G.; Björkegren, J.L.M.; Schunkert, H.; Farrall, M.; Danesh, J.; Samani, N.J.; Watkins, H.; Deloukas, P. EPIC-CVD Consortium CARDIoGRAMplusC4D; UK Biobank CardioMetabolic Consortium CHD working group. Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nat. Genet., 2017, 49(9), 1385-1391.
[http://dx.doi.org/10.1038/ng.3913] [PMID: 28714975]
Nikpay, M.; Goel, A.; Won, H.H.; Hall, L.M.; Willenborg, C.; Kanoni, S.; Saleheen, D.; Kyriakou, T.; Nelson, C.P.; Hopewell, J.C.; Webb, T.R.; Zeng, L.; Dehghan, A.; Alver, M.; Armasu, S.M.; Auro, K.; Bjonnes, A.; Chasman, D.I.; Chen, S.; Ford, I.; Franceschini, N.; Gieger, C.; Grace, C.; Gustafsson, S.; Huang, J.; Hwang, S.J.; Kim, Y.K.; Kleber, M.E.; Lau, K.W.; Lu, X.; Lu, Y.; Lyytikäinen, L.P.; Mihailov, E.; Morrison, A.C.; Pervjakova, N.; Qu, L.; Rose, L.M.; Salfati, E.; Saxena, R.; Scholz, M.; Smith, A.V.; Tikkanen, E.; Uitterlinden, A.; Yang, X.; Zhang, W.; Zhao, W.; de Andrade, M.; de Vries, P.S.; van Zuydam, N.R.; Anand, S.S.; Bertram, L.; Beutner, F.; Dedoussis, G.; Frossard, P.; Gauguier, D.; Goodall, A.H.; Gottesman, O.; Haber, M.; Han, B.G.; Huang, J.; Jalilzadeh, S.; Kessler, T.; König, I.R.; Lannfelt, L.; Lieb, W.; Lind, L.; Lindgren, C.M.; Lokki, M.L.; Magnusson, P.K.; Mallick, N.H.; Mehra, N.; Meitinger, T.; Memon, F.U.; Morris, A.P.; Nieminen, M.S.; Pedersen, N.L.; Peters, A.; Rallidis, L.S.; Rasheed, A.; Samuel, M.; Shah, S.H.; Sinisalo, J.; Stirrups, K.E.; Trompet, S.; Wang, L.; Zaman, K.S.; Ardissino, D.; Boerwinkle, E.; Borecki, I.B.; Bottinger, E.P.; Buring, J.E.; Chambers, J.C.; Collins, R.; Cupples, L.A.; Danesh, J.; Demuth, I.; Elosua, R.; Epstein, S.E.; Esko, T.; Feitosa, M.F.; Franco, O.H.; Franzosi, M.G.; Granger, C.B.; Gu, D.; Gudnason, V.; Hall, A.S.; Hamsten, A.; Harris, T.B.; Hazen, S.L.; Hengstenberg, C.; Hofman, A.; Ingelsson, E.; Iribarren, C.; Jukema, J.W.; Karhunen, P.J.; Kim, B.J.; Kooner, J.S.; Kullo, I.J.; Lehtimäki, T.; Loos, R.J.F.; Melander, O.; Metspalu, A.; März, W.; Palmer, C.N.; Perola, M.; Quertermous, T.; Rader, D.J.; Ridker, P.M.; Ripatti, S.; Roberts, R.; Salomaa, V.; Sanghera, D.K.; Schwartz, S.M.; Seedorf, U.; Stewart, A.F.; Stott, D.J.; Thiery, J.; Zalloua, P.A.; O’Donnell, C.J.; Reilly, M.P.; Assimes, T.L.; Thompson, J.R.; Erdmann, J.; Clarke, R.; Watkins, H.; Kathiresan, S.; McPherson, R.; Deloukas, P.; Schunkert, H.; Samani, N.J.; Farrall, M. A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat. Genet., 2015, 47(10), 1121-1130.
[http://dx.doi.org/10.1038/ng.3396] [PMID: 26343387]
Khera, A.V.; Kathiresan, S. Genetics of coronary artery disease: discovery, biology and clinical translation. Nat. Rev. Genet., 2017, 18(6), 331-344.
[http://dx.doi.org/10.1038/nrg.2016.160] [PMID: 28286336]
Kessler, T.; Vilne, B.; Schunkert, H. The impact of genome-wide association studies on the pathophysiology and therapy of cardiovascular disease. EMBO Mol. Med., 2016, 8(7), 688-701.
[http://dx.doi.org/10.15252/emmm.201506174] [PMID: 27189168]
CARDIoGRAMplusC4D Consortium. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat. Genet., 2013, 45(1), 25-33.
Assimes, T.L.; Roberts, R. Genetics: implications for prevention and management of coronary artery disease. J. Am. Coll. Cardiol., 2016, 68(25), 2797-2818.
[http://dx.doi.org/10.1016/j.jacc.2016.10.039] [PMID: 28007143]
Brown, M.S.; Goldstein, J.L. Familial hypercholesterolemia: A genetic defect in the low-density lipoprotein receptor. N. Engl. J. Med., 1976, 294(25), 1386-1390.
[http://dx.doi.org/10.1056/NEJM197606172942509] [PMID: 177875]
Roberts, R. PCSK9 inhibition--a new thrust in the prevention of heart disease: genetics does it again. Can. J. Cardiol., 2013, 29(8), 899-901.
[http://dx.doi.org/10.1016/j.cjca.2013.04.014] [PMID: 23809538]
Seidah, N.G.; Benjannet, S.; Wickham, L.; Marcinkiewicz, J.; Jasmin, S.B.; Stifani, S.; Basak, A.; Prat, A.; Chretien, M. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc. Natl. Acad. Sci. USA, 2003, 100(3), 928-933.
[http://dx.doi.org/10.1073/pnas.0335507100] [PMID: 12552133]
Abifadel, M.; Varret, M.; Rabès, J.P.; Allard, D.; Ouguerram, K.; Devillers, M.; Cruaud, C.; Benjannet, S.; Wickham, L.; Erlich, D.; Derré, A.; Villéger, L.; Farnier, M.; Beucler, I.; Bruckert, E.; Chambaz, J.; Chanu, B.; Lecerf, J.M.; Luc, G.; Moulin, P.; Weissenbach, J.; Prat, A.; Krempf, M.; Junien, C.; Seidah, N.G.; Boileau, C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet., 2003, 34(2), 154-156.
[http://dx.doi.org/10.1038/ng1161] [PMID: 12730697]
Cohen, J.C.; Boerwinkle, E.; Mosley, T.H., Jr; Hobbs, H.H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med., 2006, 354(12), 1264-1272.
[http://dx.doi.org/10.1056/NEJMoa054013] [PMID: 16554528]
Ni, Y.G.; Di Marco, S.; Condra, J.H.; Peterson, L.B.; Wang, W.; Wang, F.; Pandit, S.; Hammond, H.A.; Rosa, R.; Cummings, R.T.; Wood, D.D.; Liu, X.; Bottomley, M.J.; Shen, X.; Cubbon, R.M.; Wang, S.P.; Johns, D.G.; Volpari, C.; Hamuro, L.; Chin, J.; Huang, L.; Zhao, J.Z.; Vitelli, S.; Haytko, P.; Wisniewski, D.; Mitnaul, L.J.; Sparrow, C.P.; Hubbard, B.; Carfí, A.; Sitlani, A.A. PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo. J. Lipid Res., 2011, 52(1), 78-86.
[http://dx.doi.org/10.1194/jlr.M011445] [PMID: 20959675]
Stein, E.A.; Mellis, S.; Yancopoulos, G.D.; Stahl, N.; Logan, D.; Smith, W.B.; Lisbon, E.; Gutierrez, M.; Webb, C.; Wu, R.; Du, Y.; Kranz, T.; Gasparino, E.; Swergold, G.D. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N. Engl. J. Med., 2012, 366(12), 1108-1118.
[http://dx.doi.org/10.1056/NEJMoa1105803] [PMID: 22435370]
Sabatine, M.S.; Giugliano, R.P.; Keech, A.C.; Honarpour, N.; Wiviott, S.D.; Murphy, S.A.; Kuder, J.F.; Wang, H.; Liu, T.; Wasserman, S.M.; Sever, P.S.; Pedersen, T.R. FOURIER Steering Committee and Investigators Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med., 2017, 376(18), 1713-1722.
[http://dx.doi.org/10.1056/NEJMoa1615664] [PMID: 28304224]
Schwartz, G.G.; Szarek, M.; Bhatt, D.L.; Bittner, V.; Diaz, R.; Edelberg, J.; Goodman, S.G. The ODYSSEY OUTCOMES Trial: alirocumab in patients after acute coronary syndrome. american college of cardiology 67th scientific sessions, 2018. orlando, fl.
Libby, P. Interleukin-1 beta as a target for atherosclerosis therapy: biological basis of CANTOS and beyond. J. Am. Coll. Cardiol., 2017, 70(18), 2278-2289.
[http://dx.doi.org/10.1016/j.jacc.2017.09.028] [PMID: 29073957]
Hansson, G.K. Inflammation and atherosclerosis: the end of a controversy. Circulation, 2017, 136(20), 1875-1877.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.030484] [PMID: 28916641]
Ridker, P.M.; Everett, B.M.; Thuren, T.; MacFadyen, J.G.; Chang, W.H.; Ballantyne, C.; Fonseca, F.; Nicolau, J.; Koenig, W.; Anker, S.D.; Kastelein, J.J.P.; Cornel, J.H.; Pais, P.; Pella, D.; Genest, J.; Cifkova, R.; Lorenzatti, A.; Forster, T.; Kobalava, Z.; Vida-Simiti, L.; Flather, M.; Shimokawa, H.; Ogawa, H.; Dellborg, M.; Rossi, P.R.F.; Troquay, R.P.T.; Libby, P.; Glynn, R.J. CANTOS Trial Group Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med., 2017, 377(12), 1119-1131.
[http://dx.doi.org/10.1056/NEJMoa1707914] [PMID: 28845751]
Roberts, R. Mendelian randomization studies promise to shorten the journey to FDA approval. JACC Basic Transl. Sci., 2018, 3(5), 690-703.
[http://dx.doi.org/10.1016/j.jacbts.2018.08.001] [PMID: 30456340]
Voight, B.F.; Peloso, G.M.; Orho-Melander, M.; Frikke-Schmidt, R.; Barbalic, M.; Jensen, M.K.; Hindy, G.; Hólm, H.; Ding, E.L.; Johnson, T.; Schunkert, H.; Samani, N.J.; Clarke, R.; Hopewell, J.C.; Thompson, J.F.; Li, M.; Thorleifsson, G.; Newton-Cheh, C.; Musunuru, K.; Pirruccello, J.P.; Saleheen, D.; Chen, L.; Stewart, A.; Schillert, A.; Thorsteinsdottir, U.; Thorgeirsson, G.; Anand, S.; Engert, J.C.; Morgan, T.; Spertus, J.; Stoll, M.; Berger, K.; Martinelli, N.; Girelli, D.; McKeown, P.P.; Patterson, C.C.; Epstein, S.E.; Devaney, J.; Burnett, M.S.; Mooser, V.; Ripatti, S.; Surakka, I.; Nieminen, M.S.; Sinisalo, J.; Lokki, M.L.; Perola, M.; Havulinna, A.; de Faire, U.; Gigante, B.; Ingelsson, E.; Zeller, T.; Wild, P.; de Bakker, P.I.; Klungel, O.H.; Maitland-van der Zee, A.H.; Peters, B.J.; de Boer, A.; Grobbee, D.E.; Kamphuisen, P.W.; Deneer, V.H.; Elbers, C.C.; Onland-Moret, N.C.; Hofker, M.H.; Wijmenga, C.; Verschuren, W.M.; Boer, J.M.; van der Schouw, Y.T.; Rasheed, A.; Frossard, P.; Demissie, S.; Willer, C.; Do, R.; Ordovas, J.M.; Abecasis, G.R.; Boehnke, M.; Mohlke, K.L.; Daly, M.J.; Guiducci, C.; Burtt, N.P.; Surti, A.; Gonzalez, E.; Purcell, S.; Gabriel, S.; Marrugat, J.; Peden, J.; Erdmann, J.; Diemert, P.; Willenborg, C.; König, I.R.; Fischer, M.; Hengstenberg, C.; Ziegler, A.; Buysschaert, I.; Lambrechts, D.; Van de Werf, F.; Fox, K.A.; El Mokhtari, N.E.; Rubin, D.; Schrezenmeir, J.; Schreiber, S.; Schäfer, A.; Danesh, J.; Blankenberg, S.; Roberts, R.; McPherson, R.; Watkins, H.; Hall, A.S.; Overvad, K.; Rimm, E.; Boerwinkle, E.; Tybjaerg-Hansen, A.; Cupples, L.A.; Reilly, M.P.; Melander, O.; Mannucci, P.M.; Ardissino, D.; Siscovick, D.; Elosua, R.; Stefansson, K.; O’Donnell, C.J.; Salomaa, V.; Rader, D.J.; Peltonen, L.; Schwartz, S.M.; Altshuler, D.; Kathiresan, S. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet, 2012, 380(9841), 572-580.
[http://dx.doi.org/10.1016/S0140-6736(12)60312-2] [PMID: 22607825]
Teslovich, T.M.; Musunuru, K.; Smith, A.V.; Edmondson, A.C.; Stylianou, I.M.; Koseki, M.; Pirruccello, J.P.; Ripatti, S.; Chasman, D.I.; Willer, C.J.; Johansen, C.T.; Fouchier, S.W.; Isaacs, A.; Peloso, G.M.; Barbalic, M.; Ricketts, S.L.; Bis, J.C.; Aulchenko, Y.S.; Thorleifsson, G.; Feitosa, M.F.; Chambers, J.; Orho-Melander, M.; Melander, O.; Johnson, T.; Li, X.; Guo, X.; Li, M.; Shin Cho, Y.; Jin Go, M.; Jin Kim, Y.; Lee, J.Y.; Park, T.; Kim, K.; Sim, X.; Twee-Hee Ong, R.; Croteau-Chonka, D.C.; Lange, L.A.; Smith, J.D.; Song, K.; Hua Zhao, J.; Yuan, X.; Luan, J.; Lamina, C.; Ziegler, A.; Zhang, W.; Zee, R.Y.; Wright, A.F.; Witteman, J.C.; Wilson, J.F.; Willemsen, G.; Wichmann, H.E.; Whitfield, J.B.; Waterworth, D.M.; Wareham, N.J.; Waeber, G.; Vollenweider, P.; Voight, B.F.; Vitart, V.; Uitterlinden, A.G.; Uda, M.; Tuomilehto, J.; Thompson, J.R.; Tanaka, T.; Surakka, I.; Stringham, H.M.; Spector, T.D.; Soranzo, N.; Smit, J.H.; Sinisalo, J.; Silander, K.; Sijbrands, E.J.; Scuteri, A.; Scott, J.; Schlessinger, D.; Sanna, S.; Salomaa, V.; Saharinen, J.; Sabatti, C.; Ruokonen, A.; Rudan, I.; Rose, L.M.; Roberts, R.; Rieder, M.; Psaty, B.M.; Pramstaller, P.P.; Pichler, I.; Perola, M.; Penninx, B.W.; Pedersen, N.L.; Pattaro, C.; Parker, A.N.; Pare, G.; Oostra, B.A.; O’Donnell, C.J.; Nieminen, M.S.; Nickerson, D.A.; Montgomery, G.W.; Meitinger, T.; McPherson, R.; McCarthy, M.I.; McArdle, W.; Masson, D.; Martin, N.G.; Marroni, F.; Mangino, M.; Magnusson, P.K.; Lucas, G.; Luben, R.; Loos, R.J.; Lokki, M.L.; Lettre, G.; Langenberg, C.; Launer, L.J.; Lakatta, E.G.; Laaksonen, R.; Kyvik, K.O.; Kronenberg, F.; König, I.R.; Khaw, K.T.; Kaprio, J.; Kaplan, L.M.; Johansson, A.; Jarvelin, M.R.; Janssens, A.C.; Ingelsson, E.; Igl, W.; Kees Hovingh, G.; Hottenga, J.J.; Hofman, A.; Hicks, A.A.; Hengstenberg, C.; Heid, I.M.; Hayward, C.; Havulinna, A.S.; Hastie, N.D.; Harris, T.B.; Haritunians, T.; Hall, A.S.; Gyllensten, U.; Guiducci, C.; Groop, L.C.; Gonzalez, E.; Gieger, C.; Freimer, N.B.; Ferrucci, L.; Erdmann, J.; Elliott, P.; Ejebe, K.G.; Döring, A.; Dominiczak, A.F.; Demissie, S.; Deloukas, P.; de Geus, E.J.; de Faire, U.; Crawford, G.; Collins, F.S.; Chen, Y.D.; Caulfield, M.J.; Campbell, H.; Burtt, N.P.; Bonnycastle, L.L.; Boomsma, D.I.; Boekholdt, S.M.; Bergman, R.N.; Barroso, I.; Bandinelli, S.; Ballantyne, C.M.; Assimes, T.L.; Quertermous, T.; Altshuler, D.; Seielstad, M.; Wong, T.Y.; Tai, E.S.; Feranil, A.B.; Kuzawa, C.W.; Adair, L.S.; Taylor, H.A., Jr; Borecki, I.B.; Gabriel, S.B.; Wilson, J.G.; Holm, H.; Thorsteinsdottir, U.; Gudnason, V.; Krauss, R.M.; Mohlke, K.L.; Ordovas, J.M.; Munroe, P.B.; Kooner, J.S.; Tall, A.R.; Hegele, R.A.; Kastelein, J.J.; Schadt, E.E.; Rotter, J.I.; Boerwinkle, E.; Strachan, D.P.; Mooser, V.; Stefansson, K.; Reilly, M.P.; Samani, N.J.; Schunkert, H.; Cupples, L.A.; Sandhu, M.S.; Ridker, P.M.; Rader, D.J.; van Duijn, C.M.; Peltonen, L.; Abecasis, G.R.; Boehnke, M.; Kathiresan, S. Biological, clinical and population relevance of 95 loci for blood lipids. Nature, 2010, 466(7307), 707-713.
[http://dx.doi.org/10.1038/nature09270] [PMID: 20686565]
Willer, C.J.; Schmidt, E.M.; Sengupta, S.; Peloso, G.M.; Gustafsson, S.; Kanoni, S.; Ganna, A.; Chen, J.; Buchkovich, M.L.; Mora, S.; Beckmann, J.S.; Bragg-Gresham, J.L.; Chang, H.Y.; Demirkan, A.; Den Hertog, H.M.; Do, R.; Donnelly, L.A.; Ehret, G.B.; Esko, T.; Feitosa, M.F.; Ferreira, T.; Fischer, K.; Fontanillas, P.; Fraser, R.M.; Freitag, D.F.; Gurdasani, D.; Heikkilä, K.; Hyppönen, E.; Isaacs, A.; Jackson, A.U.; Johansson, Å.; Johnson, T.; Kaakinen, M.; Kettunen, J.; Kleber, M.E.; Li, X.; Luan, J.; Lyytikäinen, L.P.; Magnusson, P.K.E.; Mangino, M.; Mihailov, E.; Montasser, M.E.; Müller-Nurasyid, M.; Nolte, I.M.; O’Connell, J.R.; Palmer, C.D.; Perola, M.; Petersen, A.K.; Sanna, S.; Saxena, R.; Service, S.K.; Shah, S.; Shungin, D.; Sidore, C.; Song, C.; Strawbridge, R.J.; Surakka, I.; Tanaka, T.; Teslovich, T.M.; Thorleifsson, G.; Van den Herik, E.G.; Voight, B.F.; Volcik, K.A.; Waite, L.L.; Wong, A.; Wu, Y.; Zhang, W.; Absher, D.; Asiki, G.; Barroso, I.; Been, L.F.; Bolton, J.L.; Bonnycastle, L.L.; Brambilla, P.; Burnett, M.S.; Cesana, G.; Dimitriou, M.; Doney, A.S.F.; Döring, A.; Elliott, P.; Epstein, S.E.; Ingi Eyjolfsson, G.; Gigante, B.; Goodarzi, M.O.; Grallert, H.; Gravito, M.L.; Groves, C.J.; Hallmans, G.; Hartikainen, A.L.; Hayward, C.; Hernandez, D.; Hicks, A.A.; Holm, H.; Hung, Y.J.; Illig, T.; Jones, M.R.; Kaleebu, P.; Kastelein, J.J.P.; Khaw, K.T.; Kim, E.; Klopp, N.; Komulainen, P.; Kumari, M.; Langenberg, C.; Lehtimäki, T.; Lin, S.Y.; Lindström, J.; Loos, R.J.F.; Mach, F.; McArdle, W.L.; Meisinger, C.; Mitchell, B.D.; Müller, G.; Nagaraja, R.; Narisu, N.; Nieminen, T.V.M.; Nsubuga, R.N.; Olafsson, I.; Ong, K.K.; Palotie, A.; Papamarkou, T.; Pomilla, C.; Pouta, A.; Rader, D.J.; Reilly, M.P.; Ridker, P.M.; Rivadeneira, F.; Rudan, I.; Ruokonen, A.; Samani, N.; Scharnagl, H.; Seeley, J.; Silander, K.; Stančáková, A.; Stirrups, K.; Swift, A.J.; Tiret, L.; Uitterlinden, A.G.; van Pelt, L.J.; Vedantam, S.; Wainwright, N.; Wijmenga, C.; Wild, S.H.; Willemsen, G.; Wilsgaard, T.; Wilson, J.F.; Young, E.H.; Zhao, J.H.; Adair, L.S.; Arveiler, D.; Assimes, T.L.; Bandinelli, S.; Bennett, F.; Bochud, M.; Boehm, B.O.; Boomsma, D.I.; Borecki, I.B.; Bornstein, S.R.; Bovet, P.; Burnier, M.; Campbell, H.; Chakravarti, A.; Chambers, J.C.; Chen, Y.I.; Collins, F.S.; Cooper, R.S.; Danesh, J.; Dedoussis, G.; de Faire, U.; Feranil, A.B.; Ferrières, J.; Ferrucci, L.; Freimer, N.B.; Gieger, C.; Groop, L.C.; Gudnason, V.; Gyllensten, U.; Hamsten, A.; Harris, T.B.; Hingorani, A.; Hirschhorn, J.N.; Hofman, A.; Hovingh, G.K.; Hsiung, C.A.; Humphries, S.E.; Hunt, S.C.; Hveem, K.; Iribarren, C.; Järvelin, M.R.; Jula, A.; Kähönen, M.; Kaprio, J.; Kesäniemi, A.; Kivimaki, M.; Kooner, J.S.; Koudstaal, P.J.; Krauss, R.M.; Kuh, D.; Kuusisto, J.; Kyvik, K.O.; Laakso, M.; Lakka, T.A.; Lind, L.; Lindgren, C.M.; Martin, N.G.; März, W.; McCarthy, M.I.; McKenzie, C.A.; Meneton, P.; Metspalu, A.; Moilanen, L.; Morris, A.D.; Munroe, P.B.; Njølstad, I.; Pedersen, N.L.; Power, C.; Pramstaller, P.P.; Price, J.F.; Psaty, B.M.; Quertermous, T.; Rauramaa, R.; Saleheen, D.; Salomaa, V.; Sanghera, D.K.; Saramies, J.; Schwarz, P.E.H.; Sheu, W.H.; Shuldiner, A.R.; Siegbahn, A.; Spector, T.D.; Stefansson, K.; Strachan, D.P.; Tayo, B.O.; Tremoli, E.; Tuomilehto, J.; Uusitupa, M.; van Duijn, C.M.; Vollenweider, P.; Wallentin, L.; Wareham, N.J.; Whitfield, J.B.; Wolffenbuttel, B.H.R.; Ordovas, J.M.; Boerwinkle, E.; Palmer, C.N.A.; Thorsteinsdottir, U.; Chasman, D.I.; Rotter, J.I.; Franks, P.W.; Ripatti, S.; Cupples, L.A.; Sandhu, M.S.; Rich, S.S.; Boehnke, M.; Deloukas, P.; Kathiresan, S.; Mohlke, K.L.; Ingelsson, E.; Abecasis, G.R. Global Lipids Genetics Consortium Discovery and refinement of loci associated with lipid levels. Nat. Genet., 2013, 45(11), 1274-1283.
[http://dx.doi.org/10.1038/ng.2797] [PMID: 24097068]
Gofman, J.W.; Young, W.; Tandy, R. Ischemic heart disease, atherosclerosis, and longevity. Circulation, 1966, 34(4), 679-697.
[http://dx.doi.org/10.1161/01.CIR.34.4.679] [PMID: 5921763]
Gadi, R.; Amanullah, A.; Figueredo, V.M. HDL-C: does it matter? an update on novel HDL-directed pharmaco-therapeutic strategies. Int. J. Cardiol., 2013, 167(3), 646-655.
[http://dx.doi.org/10.1016/j.ijcard.2012.05.052] [PMID: 22668801]
Boden, W.E.; Probstfield, J.L.; Anderson, T.; Chaitman, B.R.; Desvignes-Nickens, P.; Koprowicz, K.; McBride, R.; Teo, K.; Weintraub, W. AIM-HIGH Investigators Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N. Engl. J. Med., 2011, 365(24), 2255-2267.
[http://dx.doi.org/10.1056/NEJMoa1107579] [PMID: 22085343]
Wright, R.S. Recent clinical trials evaluating benefit of drug therapy for modification of HDL cholesterol. Curr. Opin. Cardiol., 2013, 28(4), 389-398.
[http://dx.doi.org/10.1097/HCO.0b013e328362059d] [PMID: 23736814]
Lincoff, A.M.; Nicholls, S.J.; Riesmeyer, J.S.; Barter, P.J.; Brewer, H.B.; Fox, K.A.A.; Gibson, C.M.; Granger, C.; Menon, V.; Montalescot, G.; Rader, D.; Tall, A.R.; McErlean, E.; Wolski, K.; Ruotolo, G.; Vangerow, B.; Weerakkody, G.; Goodman, S.G.; Conde, D.; McGuire, D.K.; Nicolau, J.C.; Leiva-Pons, J.L.; Pesant, Y.; Li, W.; Kandath, D.; Kouz, S.; Tahirkheli, N.; Mason, D.; Nissen, S.E. ACCELERATE Investigators Evacetrapib and cardiovascular outcomes in highrisk vascular disease. N. Engl. J. Med., 2017, 376(20), 1933-1942.
[http://dx.doi.org/10.1056/NEJMoa1609581] [PMID: 28514624]
Kawashiri, M.A.; Tada, H.; Nomura, A.; Yamagishi, M. Mendelian randomization: its impact on cardiovascular disease. J. Cardiol., 2018, 72(4), 307-313.
[http://dx.doi.org/10.1016/j.jjcc.2018.04.007] [PMID: 29801689]
Barter, P.J.; Caulfield, M.; Eriksson, M.; Grundy, S.M.; Kastelein, J.J.; Komajda, M.; Lopez-Sendon, J.; Mosca, L.; Tardif, J.C.; Waters, D.D.; Shear, C.L.; Revkin, J.H.; Buhr, K.A.; Fisher, M.R.; Tall, A.R.; Brewer, B. ILLUMINATE Investigators Effects of torcetrapib in patients at high risk for coronary events. N. Engl. J. Med., 2007, 357(21), 2109-2122.
[http://dx.doi.org/10.1056/NEJMoa0706628] [PMID: 17984165]
Schwartz, G.G.; Olsson, A.G.; Abt, M.; Ballantyne, C.M.; Barter, P.J.; Brumm, J.; Chaitman, B.R.; Holme, I.M.; Kallend, D.; Leiter, L.A.; Leitersdorf, E.; McMurray, J.J.; Mundl, H.; Nicholls, S.J.; Shah, P.K.; Tardif, J.C.; Wright, R.S. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N. Engl. J. Med., 2012, 367(22), 2089-2099.
[http://dx.doi.org/10.1056/NEJMoa1206797] [PMID: 23126252]
Bowman, L.; Hopewell, J.C.; Chen, F.; Wallendszus, K.; Stevens, W.; Collins, R.; Wiviott, S.D.; Cannon, C.P.; Braunwald, E.; Sammons, E.; Landray, M.J. HPS3/TIMI55–REVEAL Collaborative Group Effects of anacetrapib in patients with atherosclerotic vascular disease. N. Engl. J. Med., 2017, 377(13), 1217-1227.
[http://dx.doi.org/10.1056/NEJMoa1706444] [PMID: 28847206]
Nomura, A.; Won, H.H.; Khera, A.V.; Takeuchi, F.; Ito, K.; McCarthy, S.; Emdin, C.A.; Klarin, D.; Natarajan, P.; Zekavat, S.M.; Gupta, N.; Peloso, G.M.; Borecki, I.B.; Teslovich, T.M.; Asselta, R.; Duga, S.; Merlini, P.A.; Correa, A.; Kessler, T.; Wilson, J.G.; Bown, M.J.; Hall, A.S.; Braund, P.S.; Carey, D.J.; Murray, M.F.; Kirchner, H.L.; Leader, J.B.; Lavage, D.R.; Manus, J.N.; Hartze, D.N.; Samani, N.J.; Schunkert, H.; Marrugat, J.; Elosua, R.; McPherson, R.; Farrall, M.; Watkins, H.; Juang, J.J.; Hsiung, C.A.; Lin, S.Y.; Wang, J.S.; Tada, H.; Kawashiri, M.A.; Inazu, A.; Yamagishi, M.; Katsuya, T.; Nakashima, E.; Nakatochi, M.; Yamamoto, K.; Yokota, M.; Momozawa, Y.; Rotter, J.I.; Lander, E.S.; Rader, D.J.; Danesh, J.; Ardissino, D.; Gabriel, S.; Willer, C.J.; Abecasis, G.R.; Saleheen, D.; Kubo, M.; Kato, N.; Ida Chen, Y.D.; Dewey, F.E.; Kathiresan, S. Proteintruncating variants at the cholesteryl ester transfer protein gene and risk for coronary heart disease. Circ. Res., 2017, 121(1), 81-88.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311145] [PMID: 28506971]
Keene, D.; Price, C.; Shun-Shin, M.J.; Francis, D.P. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients. BMJ, 2014, 349, g4379.
[http://dx.doi.org/10.1136/bmj.g4379] [PMID: 25038074]
Yang, H.T.; Lee, M.; Hong, K.S.; Ovbiagele, B.; Saver, J.L. Efficacy of folic acid supplementation in cardiovascular disease prevention: an updated meta-analysis of randomized controlled trials. Eur. J. Intern. Med., 2012, 23(8), 745-754.
[http://dx.doi.org/10.1016/j.ejim.2012.07.004] [PMID: 22884409]
Keenan, T.; Zhao, W.; Rasheed, A.; Ho, W.K.; Malik, R.; Felix, J.F.; Young, R.; Shah, N.; Samuel, M.; Sheikh, N.; Mucksavage, M.L.; Shah, O.; Li, J.; Morley, M.; Laser, A.; Mallick, N.H.; Zaman, K.S.; Ishaq, M.; Rasheed, S.Z.; Memon, F.U.; Ahmed, F.; Hanif, B.; Lakhani, M.S.; Fahim, M.; Ishaq, M.; Shardha, N.K.; Ahmed, N.; Mahmood, K.; Iqbal, W.; Akhtar, S.; Raheel, R.; O’Donnell, C.J.; Hengstenberg, C.; März, W.; Kathiresan, S.; Samani, N.; Goel, A.; Hopewell, J.C.; Chambers, J.; Cheng, Y.C.; Sharma, P.; Yang, Q.; Rosand, J.; Boncoraglio, G.B.; Kazmi, S.U.; Hakonarson, H.; Köttgen, A.; Kalogeropoulos, A.; Frossard, P.; Kamal, A.; Dichgans, M.; Cappola, T.; Reilly, M.P.; Danesh, J.; Rader, D.J.; Voight, B.F.; Saleheen, D. Causal assessment of serum urate levels in cardiometabolic diseases through a Mendelian randomization study. J. Am. Coll. Cardiol., 2016, 67(4), 407-416.
[http://dx.doi.org/10.1016/j.jacc.2015.10.086] [PMID: 26821629]
Erdmann, J.; Kessler, T.; Munoz Venegas, L.; Schunkert, H. A decade of genome-wide association studies for coronary artery disease: the challenges ahead. Cardiovasc. Res., 2018, 114(9), 1241-1257.
[http://dx.doi.org/10.1093/cvr/cvy084] [PMID: 29617720]
Goldstein, B.A.; Knowles, J.W.; Salfati, E.; Ioannidis, J.P.; Assimes, T.L. Simple, standardized incorporation of genetic risk into non-genetic risk prediction tools for complex traits: coronary heart disease as an example. Front. Genet., 2014, 5, 254.
[http://dx.doi.org/10.3389/fgene.2014.00254] [PMID: 25136350]
Fujita, H.; Okada, T.; Inami, I.; Makimoto, M.; Hosono, S.; Minato, M.; Takahashi, S.; Mugishima, H.; Yamamoto, T. Low-density lipoprotein profile changes during the neonatal period. J. Perinatol., 2008, 28(5), 335-340.
[http://dx.doi.org/10.1038/jp.2008.8] [PMID: 18337737]
Pac-Kozuchowska, E. Evaluation of lipids, lipoproteins and apolipoproteins concentrations in cord blood serum of newborns from rural and urban environments. Ann. Agric. Environ. Med., 2007, 14(1), 25-29.
[PMID: 17655173]
Swiger, KJ; Martin, SS; Blaha, MJ Narrowing sex differences in lipoprotein cholesterol subclasses following mid-life: the very large database of lipids (VLDL-10B). J. Am. Heart Assoc., 2014, 3(2), e000851.
Paynter, N.P.; Chasman, D.I.; Buring, J.E.; Shiffman, D.; Cook, N.R.; Ridker, P.M. Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3. Ann. Intern. Med., 2009, 150(2), 65-72.
[http://dx.doi.org/10.7326/0003-4819-150-2-200901200-00003] [PMID: 19153409]
Ripatti, S.; Tikkanen, E.; Orho-Melander, M.; Havulinna, A.S.; Silander, K.; Sharma, A.; Guiducci, C.; Perola, M.; Jula, A.; Sinisalo, J.; Lokki, M.L.; Nieminen, M.S.; Melander, O.; Salomaa, V.; Peltonen, L.; Kathiresan, S. A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses. Lancet, 2010, 376(9750), 1393-1400.
[http://dx.doi.org/10.1016/S0140-6736(10)61267-6] [PMID: 20971364]
Tikkanen, E.; Havulinna, A.S.; Palotie, A.; Salomaa, V.; Ripatti, S. Genetic risk prediction and a 2-stage risk screening strategy for coronary heart disease. Arterioscler. Thromb. Vasc. Biol., 2013, 33(9), 2261-2266.
[http://dx.doi.org/10.1161/ATVBAHA.112.301120] [PMID: 23599444]
Thanassoulis, G.; Peloso, G.M.; Pencina, M.J.; Hoffmann, U.; Fox, C.S.; Cupples, L.A.; Levy, D.; D’Agostino, R.B.; Hwang, S.J.; O’Donnell, C.J. A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study. Circ. Cardiovasc. Genet., 2012, 5(1), 113-121.
[http://dx.doi.org/10.1161/CIRCGENETICS.111.961342] [PMID: 22235037]
Davies, R.W.; Dandona, S.; Stewart, A.F.; Chen, L.; Ellis, S.G.; Tang, W.H.; Hazen, S.L.; Roberts, R.; McPherson, R.; Wells, G.A. Improved prediction of cardiovascular disease based on a panel of single nucleotide polymorphisms identified through genome-wide association studies. Circ. Cardiovasc. Genet., 2010, 3(5), 468-474.
[http://dx.doi.org/10.1161/CIRCGENETICS.110.946269] [PMID: 20729558]
Mega, J.L.; Stitziel, N.O.; Smith, J.G.; Chasman, D.I.; Caulfield, M.; Devlin, J.J.; Nordio, F.; Hyde, C.; Cannon, C.P.; Sacks, F.; Poulter, N.; Sever, P.; Ridker, P.M.; Braunwald, E.; Melander, O.; Kathiresan, S.; Sabatine, M.S. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet, 2015, 385(9984), 2264-2271.
[http://dx.doi.org/10.1016/S0140-6736(14)61730-X] [PMID: 25748612]
Natarajan, P.; Young, R.; Stitziel, N.O.; Padmanabhan, S.; Baber, U.; Mehran, R.; Sartori, S.; Fuster, V.; Reilly, D.F.; Butterworth, A.; Rader, D.J.; Ford, I.; Sattar, N.; Kathiresan, S. Polygenic risk score identifies subgroup with higher burden of atherosclerosis and greater relative benefit from statin therapy in the primary prevention setting. Circulation, 2017, 135(22), 2091-2101.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024436] [PMID: 28223407]
Torkamani, A.; Wineinger, N.E.; Topol, E.J. The personal and clinical utility of polygenic risk scores. Nat. Rev. Genet., 2018, 19(9), 581-590.
[http://dx.doi.org/10.1038/s41576-018-0018-x] [PMID: 29789686]
Abraham, G.; Havulinna, A.S.; Bhalala, O.G.; Byars, S.G.; De Livera, A.M.; Yetukuri, L.; Tikkanen, E.; Perola, M.; Schunkert, H.; Sijbrands, E.J.; Palotie, A.; Samani, N.J.; Salomaa, V.; Ripatti, S.; Inouye, M. Genomic prediction of coronary heart disease. Eur. Heart J., 2016, 37(43), 3267-3278.
[http://dx.doi.org/10.1093/eurheartj/ehw450] [PMID: 27655226]
Inouye, M.; Abraham, G.; Nelson, C.P.; Wood, A.M.; Sweeting, M.J.; Dudbridge, F.; Lai, F.Y.; Kaptoge, S.; Brozynska, M.; Wang, T.; Ye, S.; Webb, T.R.; Rutter, M.K.; Tzoulaki, I.; Patel, R.S.; Loos, R.J.F.; Keavney, B.; Hemingway, H.; Thompson, J.; Watkins, H.; Deloukas, P.; Di Angelantonio, E.; Butterworth, A.S.; Danesh, J.; Samani, N.J. UK Biobank CardioMetabolic Consortium CHD Working Group. Genomic risk prediction of coronary artery disease in 480,000 adults. J. Am. Coll. Cardiol., 2018, 72(16), 1883-1893.
[http://dx.doi.org/10.1016/j.jacc.2018.07.079] [PMID: 30309464]
Vilhjálmsson, B.J.; Yang, J.; Finucane, H.K.; Gusev, A.; Lindström, S.; Ripke, S.; Genovese, G.; Loh, P.R.; Bhatia, G.; Do, R.; Hayeck, T.; Won, H.H.; Kathiresan, S.; Pato, M.; Pato, C.; Tamimi, R.; Stahl, E.; Zaitlen, N.; Pasaniuc, B.; Belbin, G.; Kenny, E.E.; Schierup, M.H.; De Jager, P.; Patsopoulos, N.A.; McCarroll, S.; Daly, M.; Purcell, S.; Chasman, D.; Neale, B.; Goddard, M.; Visscher, P.M.; Kraft, P.; Patterson, N.; Price, A.L. Schizophrenia Working Group of the Psychiatric Genomics Consortium Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) study. Modeling linkage disequilibrium increases accuracy of polygenic risk scores. Am. J. Hum. Genet., 2015, 97(4), 576-592.
[http://dx.doi.org/10.1016/j.ajhg.2015.09.001] [PMID: 26430803]
Khera, A.V.; Chaffin, M.; Aragam, K.G.; Haas, M.E.; Roselli, C.; Choi, S.H.; Natarajan, P.; Lander, E.S.; Lubitz, S.A.; Ellinor, P.T.; Kathiresan, S. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat. Genet., 2018, 50(9), 1219-1224.
[http://dx.doi.org/10.1038/s41588-018-0183-z] [PMID: 30104762]
Zhang, Y.; Qi, G.; Park, J-H.; Chatterjee, N. Estimation of complex effect-size distributions using summary-level statistics from genome-wide association studies across 32 complex traits. Nat. Genet., 2018, 50(9), 1318-1326.
[http://dx.doi.org/10.1038/s41588-018-0193-x] [PMID: 30104760]
Khera, A.V.; Emdin, C.A.; Drake, I.; Natarajan, P.; Bick, A.G.; Cook, N.R.; Chasman, D.I.; Baber, U.; Mehran, R.; Rader, D.J.; Fuster, V.; Boerwinkle, E.; Melander, O.; Orho-Melander, M.; Ridker, P.M.; Kathiresan, S. Genetic risk, adherence to a healthy lifestyle, and coronary disease. N. Engl. J. Med., 2016, 375(24), 2349-2358.
[http://dx.doi.org/10.1056/NEJMoa1605086] [PMID: 27959714]
Tikkanen, E.; Gustafsson, S.; Ingelsson, E. Associations of fitness, physical activity, strength, and genetic risk with cardiovascular disease: longitudinal analyses in the UK Biobank study. Circulation, 2018, 137(24), 2583-2591.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032432] [PMID: 29632216]
Marston, N.A.; Kamanu, F.K.; Nordio, F.; Gurmu, Y.; Roselli, C.; Sever, P.S.; Pedersen, T.R.; Keech, A.C.; Wang, H.; Lira Pineda, A.; Giugliano, R.P.; Lubitz, S.A.; Ellinor, P.T.; Sabatine, M.S.; Ruff, C.T. Predicting benefit from evolocumab therapy in patients with atherosclerotic disease using a genetic risk score: Results From the FOURIER Trial. Circulation, 2020, 141(8), 616-623.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043805] [PMID: 31707849]
Damask, A.; Steg, P.G.; Schwartz, G.G.; Szarek, M.; Hagström, E.; Badimon, L.; Chapman, M.J.; Boileau, C.; Tsimikas, S.; Ginsberg, H.N.; Banerjee, P.; Manvelian, G.; Pordy, R.; Hess, S.; Overton, J.D.; Lotta, L.A.; Yancopoulos, G.D.; Abecasis, G.R.; Baras, A.; Paulding, C. Regeneron genetics center and the ODYSSEY OUTCOMES investigators. Patients with high genome-wide polygenic risk scores for coronary artery disease may receive greater clinical benefit from alirocumab treatment in the ODYSSEY OUTCOMES trial. Circulation, 2020, 141(8), 624-636.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044434] [PMID: 31707832]
Elliott, J.; Bodinier, B.; Bond, T.A.; Chadeau-Hyam, M.; Evangelou, E.; Moons, K.G.M.; Dehghan, A.; Muller, D.C.; Elliott, P.; Tzoulaki, I. Predictive accuracy of a polygenic risk score-enhanced prediction model vs a clinical risk score for coronary artery disease. JAMA, 2020, 323(7), 636-645.
[http://dx.doi.org/10.1001/jama.2019.22241] [PMID: 32068818]
Mosley, J.D.; Gupta, D.K.; Tan, J.; Yao, J.; Wells, Q.S.; Shaffer, C.M.; Kundu, S.; Robinson-Cohen, C.; Psaty, B.M.; Rich, S.S.; Post, W.S.; Guo, X.; Rotter, J.I.; Roden, D.M.; Gerszten, R.E.; Wang, T.J. Predictive accuracy of a polygenic risk score compared with a clinical risk score for incident coronary heart disease. JAMA, 2020, 323(7), 627-635.
[http://dx.doi.org/10.1001/jama.2019.21782] [PMID: 32068817]
Khan, S.S.; Cooper, R.; Greenland, P. Do polygenic risk scores improve patient selection for prevention of coronary artery disease? JAMA, 2020, 323(7), 614-615.
[http://dx.doi.org/10.1001/jama.2019.21667] [PMID: 32068803]
Roberts, R. Genetic risk stratification: tipping point for global primary prevention of coronary artery disease. Circulation, 2018, 137(24), 2554-2556.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034732] [PMID: 29891617]
Manolio, T.A.; Collins, F.S. The HapMap and genome-wide association studies in diagnosis and therapy. Annu. Rev. Med., 2009, 60(1), 443-456.
[http://dx.doi.org/10.1146/annurev.med.60.061907.093117] [PMID: 19630580]
Baigent, C.; Blackwell, L.; Emberson, J.; Holland, L.E.; Reith, C.; Bhala, N.; Peto, R.; Barnes, E.H.; Keech, A.; Simes, J.; Collins, R. Cholesterol Treatment Trialists’ (CTT) Collaboration Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet, 2010, 376(9753), 1670-1681.
[http://dx.doi.org/10.1016/S0140-6736(10)61350-5] [PMID: 21067804]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [382 - 398]
Pages: 17
DOI: 10.2174/1389202921999200630145241
Price: $65

Article Metrics

PDF: 38