Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease
Open accessAbstract
BACKGROUND: A low plasma level of low-density lipoprotein (LDL) cholesterol is associated with reduced risk of coronary heart disease (CHD), but the effect of lifelong reductions in plasma LDL cholesterol is not known. We examined the effect of DNA-sequence variations that reduce plasma levels of LDL cholesterol on the incidence of coronary events in a large population. METHODS: We compared the incidence of CHD (myocardial infarction, fatal CHD, or coronary revascularization) over a 15-year interval in the Atherosclerosis Risk in Communities study according to the presence or absence of sequence variants in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) that are associated with reduced plasma levels of LDL cholesterol. RESULTS: Of the 3363 black subjects examined, 2.6 percent had nonsense mutations in PCSK9; these mutations were associated with a 28 percent reduction in mean LDL cholesterol and an 88 percent reduction in the risk of CHD (P=0.008 for the reduction; hazard ratio, 0.11; 95 percent confidence interval, 0.02 to 0.81; P=0.03). Of the 9524 white subjects examined, 3.2 percent had a sequence variation in PCSK9 that was associated with a 15 percent reduction in LDL cholesterol and a 47 percent reduction in the risk of CHD (hazard ratio, 0.50; 95 percent confidence interval, 0.32 to 0.79; P=0.003). CONCLUSIONS: These data indicate that moderate lifelong reduction in the plasma level of LDL cholesterol is associated with a substantial reduction in the incidence of coronary events, even in populations with a high prevalence of non-lipid-related cardiovascular risk factors.
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PCSK9 promotes degradation of LDL receptors, thereby diminishing the clearance of LDL from the circulation.
“Proprotein convertase subtilisin-kexin type 9 (PCSK9) promotes degradation of LDL receptors, thereby diminishing the clearance of LDL from the circulation. 6”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [6]
The Conclusions section says that PCSK9 overexpression in mice markedly reduces hepatic LDL receptors, the main pathway for removing LDL from plasma, and raises circulating LDL cholesterol. It also says mice lacking PCSK9 have more hepatic LDL receptors and clear LDL faster. This supports the receptor-and-clearance relationship, but our copy does not specify that PCSK9 reduces receptors by promoting their degradation. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLoss-of-function mutations in PCSK9 are causatively associated with lifelong reductions in LDL-C and lower coronary heart disease risk.
“In 2005, a causative association was established between the presence of loss-of-function mutations in PCSK9 and lifelong reductions in LDL-C associated with lower CHD risk (3).”
From PCSK9 and the nervous system: a no-brainer? (2023) · cites this paper as [3]
The Discussion reports that LDL-lowering PCSK9 variants were associated with substantially lower CHD incidence and suggests that lifelong LDL reduction explains the large benefit. It does not establish the claimed causal pathway: the authors acknowledge that the variants might reduce CHD through a mechanism unrelated to LDL lowering. The cited paper was published in 2006, not 2005. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCarriage of PCSK9 loss-of-function alleles is associated with lower LDL cholesterol levels and a reduced risk of myocardial infarction.
“Genetic studies have shown that carriage of PCSK9 loss-of-function alleles is associated with lower LDL cholesterol levels and a reduced risk of myocardial infarction.7,8”
From Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease (2017) · cites this paper as [7]
The Discussion (page unavailable) reports that LDL-lowering PCSK9 variants were associated with reduced coronary heart disease. The Methods (page unavailable) define that outcome as a composite including myocardial infarction, CHD death, and coronary revascularization; the paper does not report a separate reduction in myocardial infarction risk. (LLM, conf=0.85)
Experimental — accuracy not yet measuredDrugs that reduce LDL-C predominantly through upregulation of LDL receptor expression should, barring off-target adverse effects, lead to clinical benefit in proportion to the degree of LDL-C reduction.
“These data suggest that drugs that ultimately reduce LDL-C level predominantly through upregulation of LDL receptor expression should, barring any off-target adverse effects, lead to clinical benefit in proportion to the degree of LDL-C reduction.64”
From Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis (2016) · cites this paper as [64]
The Discussion reports that coronary-event reductions in clinical trials were directly related to the magnitude of LDL-C reduction, and the passage on statin treatment (p. 1272) says statins increase LDL-receptor gene expression. The paper does not establish that this relationship applies to drugs generally when they predominantly act through LDL-receptor upregulation, or assess the off-target-effects condition. (LLM, conf=0.82)
Experimental — accuracy not yet measuredSome of the most important human metabolic disease genes have been identified using germline genetic methods such as GWAS and whole exome sequencing.
“Some of the most important human metabolic disease genes have been identified using germline genetic methods such as GWAS and whole exome sequencing42-44.”
From Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease (2023) · cites this paper as [44]
The Methods and Results describe a study of inherited PCSK9 variants associated with lower LDL cholesterol and reduced coronary heart disease risk. The Genotyping section specifies targeted TaqMan assays for known variants; the paper does not say that PCSK9 was identified by GWAS or whole-exome sequencing. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Loss-of-function mutations in PCSK9 result in lower LDL cholesterol levels, which are associated with a lower risk of incident coronary heart disease.
“mutations conveying gain or loss of function of PCSK9 result in a higher or lower level of LDL cholesterol, respectively, which in turn is associated with a corresponding higher 7 or lower 6 risk of incident coronary heart disease.”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [6]
PCSK9 loss-of-function mutation carriers with lifelong reductions in LDL-C and coronary heart disease incidence were not initially found at significantly reduced risk of stroke.
“Whereas PCSK9 loss-of-function mutations carriers with lifelong reductions in LDL-C and coronary heart disease incidence, were not initially found at significantly reduced risk of stroke (3, 72), a much larger study of the UK Biobank database described the first genetic evidence of a protective effect of the R46L loss-of-function mutation on PCSK9 on ischemic stroke (73).”
From PCSK9 and the nervous system: a no-brainer? (2023) · cites this paper as [3]
Lowering LDL-C reduces atherosclerotic cardiovascular disease risk proportionally to the absolute achieved reduction in LDL-C.
“and that lowering LDL-C reduces the risk of ASCVD proportionally to the absolute achieved reduction in LDL-C [2,51].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [51]
LDL-C is causally associated with atherosclerotic cardiovascular disease risk.
“The remarkable consistency among these studies, in addition to biological and experimental evidence, provides compelling evidence that LDL-C is causally associated with the risk of ASCVD”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [51]
Because both PCSK9 outcome trials had relatively short follow-up and statin trials indicate clinical benefits of LDL-lowering may emerge only after about 1 year, these trials may have underestimated the impact of longer-term treatment.
“Both studies had relatively short follow-up periods and the evidence from statin trials indicates that the clinical benefits of LDL-lowering may only emerge after about 1 year [51], so these trials may have underestimated the potential impact of longer-term treatment [120,290].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [51]
These developments have enabled researchers to bridge the gap between monogenic and polygenic realms, identifying common variant modifiers of monogenic phenotypes and low-frequency and rare variants influencing common multifactorial traits.
“These developments have enabled researchers to bridge the gap between the monogenic and polygenic realms, identifying common variant modifiers of monogenic phenotypes contributing to the variable expression of rare, large-effect alleles26,93, and low-frequency and rare variants that influence common multifactorial traits94,95.”
From A brief history of human disease genetics (2020) · cites this paper as [95]
Not only the magnitude of LDL-C lowering is important, but the duration of exposure to elevated LDL-C levels is equally important.
“At the same time, it has become increasingly evident now that not only the magnitude of LDL-C lowering is important but that the duration of exposure to elevated LDL-C levels is equally important [11,16,38].”
The duration of exposure to low LDL-C levels may be as important as the magnitude of LDL-C lowering.
“Additionally, increasing evidence also suggests that the duration of exposure to low LDL-C levels may be as important as the magnitude of LDL-C lowering [11][12][13][14][15][16].”
Exceptionally low rates of CV events are observed in patients carrying mutations in PCSK9 or other similar genes despite only modestly low LDL-C levels.
“The exceptionally low rates of CV events observed in patients carrying mutations in PCSK9 or other similar genes despite only modestly low LDL-C levels strongly support this notion [11].”
Hobbs and Cohen identified low-frequency common variants in PCSK9 at 0.5 to 1%, which allowed epidemiological research documenting a protective effect on myocardial infarction.
“Hobbs and Cohen sequenced the gene (126, 127) and identified low-frequency common variants (0.5 to 1%), which allowed epidemiological research documenting a protective effect on myocardial infarction (128).”
From Genetic Mapping in Human Disease (2008) · cites this paper as [128]
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Cites
Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944 · see citing works
Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)
Grundy, S. M., Becker, D. M., Clark, L. T., Cooper, R., Denke, M. A., Howard, J. L., Hunninghake, D. B., Illingworth, D. R., Luepker, R. V., McBride, P. E., et al. (2002) · Civil War Book Review · Cited by 12,198 · see citing works
THE ATHEROSCLEROSIS RISK IN COMMUNIT (ARIC) STUDY: DESIGN AND OBJECTIVES
THE ARIC INVESTIGATORS (1989) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a115184 · Cited by 3,491 · see citing works
(1989) · PubMed · Cited by 3,139 · see citing works
Stamler, J. (1986) · JAMA · doi:10.1001/jama.256.20.2823 · Cited by 1,996 · see citing works
Law, M. R., Wald, N. J., & Rudnicka, A. R. (2003) · BMJ · doi:10.1136/bmj.326.7404.1423 · Cited by 1,720 · see citing works
Cohen, J., Pertsemlidis, A., Kotowski, I. K., Graham, R., Garcia, C. K., & Hobbs, H. H. (2005) · Nature Genetics · doi:10.1038/ng1509 · Cited by 1,381 · see citing works
Self-citationSeidah, N. G., Benjannet, S., Wickham, L., Marcinkiewicz, J., Jasmin, S. B., Stifani, S., Basak, A., Prat, A., & Chrétien, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0335507100 · Cited by 1,191 · see citing works
CORONARY DISEASE AMONG UNITED STATES SOLDIERS KILLED IN ACTION IN KOREA
Enos, W. F. (1953) · JAMA · doi:10.1001/jama.1953.03690120006002 · Cited by 890 · see citing works
Decreased plasma cholesterol and hypersensitivity to statins in mice lacking <i>Pcsk9</i>
Rashid, S., Curtis, D. E., Garuti, R., Anderson, N. N., Bashmakov, Y., Ho, Y. K., Hammer, R. E., Moon, Y.-A., & Horton, J. D. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501652102 · Cited by 679 · see citing works
Claudio Napoli, A., Glass, C. K., Witztum, J. L., Deutsch, R., D’Armiento, F. P., & Palinski, W. (1999) · The Lancet · doi:10.1016/s0140-6736(99)02131-5 · Cited by 645 · see citing works
NARC-1/PCSK9 and Its Natural Mutants
Benjannet, S., Rhainds, D., Essalmani, R., Mayne, J., Wickham, L., Jin, W., Asselin, M.-C., Hamelin, J., Varret, M., Allard, D., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409699200 · Cited by 628 · see citing works
Dubuc, G., Chamberland, A., Wassef, H., Davignon, J., Seidah, N. G., Bernier, L., & Prat, A. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000134621.14315.43 · Cited by 614 · see citing works
Maxwell, K. N., & Breslow, J. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402133101 · Cited by 613 · see citing works
Coronary Artery Disease in Combat Casualties in Vietnam
McNamara, J. (1971) · JAMA · doi:10.1001/jama.1971.03180330061012 · Cited by 607 · see citing works
Determinants of atherosclerosis in the young
McGill, H. C., & McMahan, C. A. (1998) · The American Journal of Cardiology · doi:10.1016/s0002-9149(98)00720-6 · Cited by 538 · see citing works
Chen, Z., Peto, R., Collins, R., MacMahon, S. W., Lu, J., & Li, W. (1991) · BMJ · doi:10.1136/bmj.303.6797.276 · Cited by 537 · see citing works
A Spectrum of PCSK9 Alleles Contributes to Plasma Levels of Low-Density Lipoprotein Cholesterol
Kotowski, I. K., Pertsemlidis, A., Luke, A., Cooper, R. S., Vega, G. L., Cohen, J. C., & Hobbs, H. H. (2006) · The American Journal of Human Genetics · doi:10.1086/500615 · Cited by 517 · see citing works
Self-citationPark, S. W., Moon, Y.-A., & Horton, J. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410077200 · Cited by 500 · see citing works
Coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC) study
Chambless, L. E., Folsom, A. R., Sharrett, A. R., Sorlie, P. D., Couper, D. J., Szklo, M., & Nieto, F. J. (2003) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(03)00055-6 · Cited by 305 · see citing works
Bond, M. G., Barnes, R. W., Riley, W. A., Wilmoth, S. K., Chambless, L. E., Howard, G., Owens, B., & The ARIC Study Group (1991) · Journal of Neuroimaging · doi:10.1111/jon19911268 · Cited by 254 · see citing works
Brown, S. A., Hutchinson, R. G., Morrisett, J. D., Boerwinkle, E., DAVIS, C. E., Gotto, A. M., & Patsch, W. (1993) · Arteriosclerosis and Thrombosis A Journal of Vascular Biology · doi:10.1161/01.atv.13.8.1139 · Cited by 207 · see citing works
Self-citationCoronary artery disease in combat casualties in Vietnam
McNamara, J. J. (1971) · JAMA · doi:10.1001/jama.216.7.1185 · Cited by 130 · see citing works
Lalanne, F., Lambert, G., Amar, M. J. A., Chétiveaux, M., Zaïr, Y., Jarnoux, A.-L., Ouguerram, K., Friburg, J., Seidah, N. G., Brewer, H. B., et al. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m400396-jlr200 · Cited by 104 · see citing works
Starting Earlier to Prevent Heart Disease
McGill, H. C., & McMahan, C. A. (2003) · JAMA · doi:10.1001/jama.290.17.2320 · Cited by 82 · see citing works
Welty, F. K., Ordovás, J. M., Schaefer, E. J., et al. (1995) · Circulation · doi:10.1161/01.cir.92.8.2036 · Cited by 37 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [9]9. convertase subtilisin/kexin type 9a in mouse liver. J Biol Chem 2004;279:50630-8.
- [17]17. heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA 1986;256:2823-8.
Cited by
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The mutational constraint spectrum quantified from variation in 141,456 humans
Karczewski, K. J., Francioli, L. C., Tiao, G., Cummings, B. B., Alföldi, J., Wang, Q., Collins, R. L., Laricchia, K. M., Ganna, A., Birnbaum, D. P., et al. (2020) · Nature · doi:10.1038/s41586-020-2308-7 · Cited by 9,434 · see citing works
Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association
Virani, S. S., Alonso, A., Benjamin, E. J., Bittencourt, M. S., Callaway, C. W., Carson, A. P., Chamberlain, A. M., Chang, A. R., Cheng, S., Delling, F. N., et al. (2020) · Circulation · doi:10.1161/cir.0000000000000757 · Cited by 9,175 · see citing works
Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association
Benjamin, E. J., Muntner, P., Alonso, A., Bittencourt, M. S., Callaway, C. W., Carson, A. P., Chamberlain, A. M., Chang, A. R., Cheng, S., Das, S. R., et al. (2019) · Circulation · doi:10.1161/cir.0000000000000659 · Cited by 9,036 · see citing works
Verbanck, M., Chen, C.-Y., Neale, B., & Do, R. (2018) · Nature Genetics · doi:10.1038/s41588-018-0099-7 · Cited by 8,591 · see citing works
A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium (2010) · Nature · doi:10.1038/nature09534 · Cited by 7,877 · see citing works
Heart disease and stroke statistics-2018 update: a report from the american heart association
Benjamin, E. J., Virani, S. S., Callaway, C. W., Chamberlain, A. M., Chang, A. R., Cheng, S., Chiuve, S. E., Cushman, M., Delling, F. N., Deo, R., et al. (2018) · Circulation · doi:10.1161/cir.0000000000000558 · Cited by 7,146 · see citing works
Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease
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., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1615664 · Cited by 6,138 · see citing works
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854 · see citing works
Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians
Davies, N. M., Holmes, M. V., & Davey Smith, G. (2018) · BMJ · doi:10.1136/bmj.k601 · Cited by 4,404 · see citing works
Ference, B. A., Ginsberg, H. N., Graham, I., Ray, K. K., Packard, C. J., Bruckert, E., Hegele, R. A., Krauss, R. M., Raal, F. J., Schunkert, H., et al. (2017) · European Heart Journal · doi:10.1093/eurheartj/ehx144 · Cited by 3,962 · see citing works
Progress and challenges in translating the biology of atherosclerosis
Libby, P., Ridker, P. M., & Hansson, G. K. (2011) · Nature · doi:10.1038/nature10146 · Cited by 4,010 · see citing works
Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome
Schwartz, G. G., Steg, P. G., Szarek, M., Bhatt, D. L., Bittner, V. A., Diaz, R., Edelberg, J. M., Goodman, S. G., Hanotin, C., Harrington, R. A., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1801174 · Cited by 3,634 · see citing works
Heidenreich, P. A., Trogdon, J. G., Khavjou, O. A., Butler, J., Dracup, K., Ezekowitz, M. D., Finkelstein, E. A., Hong, Y., Johnston, S. C., Khera, A., et al. (2011) · Circulation · doi:10.1161/cir.0b013e31820a55f5 · Cited by 3,208 · see citing works
Libby, P., Buring, J. E., Badimon, L., Hansson, G. K., Deanfield, J., Bittencourt, M. S., Tokgözoğlu, L., & Lewis, E. F. (2019) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0106-z · Cited by 3,211 · see citing works
Endothelial Function and Dysfunction: Testing and Clinical Relevance
Deanfield, J. E., Halcox, J. P., & Rabelink, T. J. (2007) · Circulation · doi:10.1161/circulationaha.106.652859 · Cited by 2,710 · see citing works
A comprehensive 1000 Genomes–based genome-wide association meta-analysis of coronary artery disease
the CARDIoGRAMplusC4D Consortium (2015) · Nature Genetics · doi:10.1038/ng.3396 · Cited by 2,447 · see citing works
Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events
Robinson, J. G., Farnier, M., Krempf, M., Bergeron, J., Luc, G., Averna, M., Stroes, E. S., Langslet, G., Raal, F. J., El Shahawy, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501031 · Cited by 2,296 · see citing works
Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002 · see citing works
The mutational constraint spectrum quantified from variation in 141,456 humans
Karczewski, K. J., Francioli, L. C., Tiao, G., Cummings, B. B., Alföldi, J., Wang, Q., Collins, R. L., Laricchia, K. M., Ganna, A., Birnbaum, D. P., et al. (2019) · doi:10.1101/531210 · Cited by 1,662 · see citing works
A Common Allele on Chromosome 9 Associated with Coronary Heart Disease
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., et al. (2007) · Science · doi:10.1126/science.1142447 · Cited by 1,587 · see citing works
Self-citationEfficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events
Sabatine, M. S., Giugliano, R. P., Wiviott, S. D., Raal, F. J., Blom, D. J., Robinson, J., Ballantyne, C. M., Somaratne, R., Legg, J., Wasserman, S. M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500858 · Cited by 1,509 · see citing works
Silverman, M. G., Ference, B. A., Im, K., Wiviott, S. D., Giugliano, R. P., Grundy, S. M., Braunwald, E., & Sabatine, M. S. (2016) · JAMA · doi:10.1001/jama.2016.13985 · Cited by 1,483 · see citing works
Triglycerides and cardiovascular disease
Nordestgaard, B. G., & Varbo, A. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61177-6 · Cited by 1,419 · see citing works
Genetic Mapping in Human Disease
Altshuler, D., Daly, M. J., & Lander, E. S. (2008) · Science · doi:10.1126/science.1156409 · Cited by 1,452 · see citing works
Tabas, I., Williams, K. J., & Borén, J. (2007) · Circulation · doi:10.1161/circulationaha.106.676890 · Cited by 1,399 · see citing works
Kathiresan, S., Melander, O., Guiducci, C., Surti, A., Burtt, N. P., Rieder, M. J., Cooper, G. M., Roos, C., Voight, B. F., Havulinna, A. S., et al. (2008) · Nature Genetics · doi:10.1038/ng.75 · Cited by 1,386 · see citing works
Common variants at 30 loci contribute to polygenic dyslipidemia
Kathiresan, S., Willer, C. J., Peloso, G. M., Demissie, S., Musunuru, K., Schadt, E. E., Kaplan, L., Bennett, D., Li, Y., Tanaka, T., et al. (2009) · Nature Genetics · doi:10.1038/ng.291 · Cited by 1,364 · see citing works
A Century of Cholesterol and Coronaries: From Plaques to Genes to Statins
Goldstein, J. L., & Brown, M. S. (2015) · Cell · doi:10.1016/j.cell.2015.01.036 · Cited by 1,233 · see citing works
Remnant Cholesterol as a Causal Risk Factor for Ischemic Heart Disease
Varbo, A., Benn, M., Tybjærg-Hansen, A., Jørgensen, A. B., Frikke-Schmidt, R., & Nordestgaard, B. G. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.08.1026 · Cited by 1,115 · see citing works
Myocardial Infarction Genetics Consortium (2009) · Nature Genetics · doi:10.1038/ng.327 · Cited by 1,088 · see citing works
Loss-of-Function Mutations in <i>APOC3,</i> Triglycerides, and Coronary Disease
The TG and HDL Working Group of the Exome Sequencing Project, N. H. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1307095 · Cited by 1,071 · see citing works
Integrated detection and population-genetic analysis of SNPs and copy number variation
McCarroll, S. A., Kuruvilla, F. G., Korn, J. M., Cawley, S., Nemesh, J., Wysoker, A., Shapero, M. H., de Bakker, P. I. W., Maller, J. B., Kirby, A., et al. (2008) · Nature Genetics · doi:10.1038/ng.238 · Cited by 936 · see citing works
Ference, B. A., Yoo, W., Alesh, I., Mahajan, N., Mirowska, K. K., Mewada, A., Kahn, J., Afonso, L., Williams, K. A., & Flack, J. M. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.09.017 · Cited by 898 · see citing works
Common variants associated with plasma triglycerides and risk for coronary artery disease
Do, R., Willer, C. J., Schmidt, E. M., Sengupta, S., Gao, C., Peloso, G. M., Gustafsson, S., Kanoni, S., Ganna, A., Chen, J., et al. (2013) · Nature Genetics · doi:10.1038/ng.2795 · Cited by 862 · see citing works
Self-citationInclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia
Raal, F. J., Kallend, D., Ray, K. K., Turner, T., Koenig, W., Wright, R. S., Wijngaard, P. L. J., Curcio, D., Jaros, M. J., Leiter, L. A., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1913805 · Cited by 818 · see citing works
Genetics of 35 blood and urine biomarkers in the UK Biobank
Sinnott-Armstrong, N., Tanigawa, Y., Amar, D., Mars, N., Benner, C., Aguirre, M., Venkataraman, G. R., Wainberg, M., Ollila, H. M., Kiiskinen, T., et al. (2021) · Nature Genetics · doi:10.1038/s41588-020-00757-z · Cited by 744 · see citing works
In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates
Musunuru, K., Chadwick, A. C., Mizoguchi, T., Garcia, S. P., DeNizio, J. E., Reiss, C. W., Wang, K., Iyer, S., Dutta, C., Clendaniel, V., et al. (2021) · Nature · doi:10.1038/s41586-021-03534-y · Cited by 793 · see citing works
National Institute of Diabetes and Digestive Kidney Diseases Inflammatory Bowel Disease Genetics Consortium (NIDDK IBDGC), Rivas, M. A., United Kingdom Inflammatory Bowel Disease Genetics Consortium, International Inflammatory Bowel Disease Genetics Consortium, Beaudoin, M., Gardet, A., Stevens, C., Sharma, Y., Zhang, C. K., Boucher, G., et al. (2011) · Nature Genetics · doi:10.1038/ng.952 · Cited by 771 · see citing works
Variation in<i>PCSK9</i>and<i>HMGCR</i>and Risk of Cardiovascular Disease and Diabetes
Ference, B. A., Robinson, J. G., Brook, R. D., Catapano, A. L., Chapman, M. J., Neff, D. R., Voros, S., Giugliano, R. P., Davey Smith, G., Fazio, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1604304 · Cited by 743 · see citing works
National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2
Jacobson, T. A., Maki, K. C., Orringer, C. E., Jones, P. H., Kris-Etherton, P., Sikand, G., La Forge, R., Daniels, S. R., Wilson, D. P., Morris, P. B., et al. (2015) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2015.09.002 · Cited by 784 · see citing works
Validating therapeutic targets through human genetics
Plenge, R. M., Scolnick, E. M., & Altshuler, D. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4051 · Cited by 712 · see citing works
Viney, N. J., van Capelleveen, J. C., Geary, R. S., Xia, S., Tami, J. A., Yu, R. Z., Marcovina, S. M., Hughes, S. G., Graham, M. J., Crooke, R. M., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31009-1 · Cited by 754 · see citing works
A brief history of human disease genetics
Claussnitzer, M., Cho, J. H., Collins, R., Cox, N. J., Dermitzakis, E. T., Hurles, M. E., Kathiresan, S., Kenny, E. E., Lindgren, C. M., MacArthur, D. G., et al. (2020) · Nature · doi:10.1038/s41586-019-1879-7 · Cited by 697 · see citing works
Pooled Association Tests for Rare Variants in Exon-Resequencing Studies
Price, A. L., Kryukov, G. V., de Bakker, P. I. W., Purcell, S. M., Staples, J., Wei, L.-J., & Sunyaev, S. R. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.04.005 · Cited by 755 · see citing works
Polymorphisms Associated with Cholesterol and Risk of Cardiovascular Events
Kathiresan, S., Melander, O., Anevski, D., Guiducci, C., Burtt, N. P., Roos, C., Hirschhorn, J. N., Berglund, G., Hedblad, B., Groop, L., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0706728 · Cited by 696 · see citing works
King, E. A., Davis, J. W., & Degner, J. F. (2019) · PLOS Genetics · doi:10.1371/journal.pgen.1008489 · Cited by 649 · see citing works
Pollin, T. I., Damcott, C. M., Shen, H., Ott, S. H., Shelton, J., Horenstein, R. B., Post, W., McLenithan, J. C., Bielak, L. F., Peyser, P. A., et al. (2008) · Science · doi:10.1126/science.1161524 · Cited by 688 · see citing works
Mendelian randomization in cardiometabolic disease: challenges in evaluating causality
Holmes, M. V., Ala-Korpela, M., & Smith, G. D. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.78 · Cited by 679 · see citing works
Engineered Virus-like Particles for Efficient in Vivo Delivery of Therapeutic Proteins
Banskota, S., Raguram, A., Suh, S., Du, S. W., Davis, J. R., Choi, E. H., Wang, X., Nielsen, S. C., Newby, G. A., Randolph, P. B., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.021 · Cited by 668 · see citing works
C Reactive Protein Coronary Heart Disease Genetics Collaboration (CCGC) (2011) · BMJ · doi:10.1136/bmj.d548 · Cited by 642 · see citing works
Common vs. rare allele hypotheses for complex diseases
Schork, N. J., Murray, S. S., Frazer, K. A., & Topol, E. J. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.04.010 · Cited by 649 · see citing works
Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol
Stein, E. A., Mellis, S., Yancopoulos, G. D., Stahl, N., Logan, D., Smith, W. B., Lisbon, E., Gutierrez, M., Webb, C., Wu, R., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1105803 · Cited by 664 · see citing works
Genetics of coronary artery disease: discovery, biology and clinical translation
Khera, A. V., & Kathiresan, S. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2016.160 · Cited by 659 · see citing works
Exome sequencing and characterization of 49,960 individuals in the UK Biobank
Van Hout, C. V., Tachmazidou, I., Backman, J. D., Hoffman, J. D., Liu, D., Pandey, A. K., Gonzaga-Jauregui, C., Khalid, S., Ye, B., Banerjee, N., et al. (2020) · Nature · doi:10.1038/s41586-020-2853-0 · Cited by 561 · see citing works
Searching for missing heritability: Designing rare variant association studies
Zuk, O., Schaffner, S. F., Samocha, K., Do, R., Hechter, E., Kathiresan, S., Daly, M. J., Neale, B. M., Sunyaev, S. R., & Lander, E. S. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322563111 · Cited by 635 · see citing works
Copy-number variation and association studies of human disease
McCarroll, S. A., & Altshuler, D. M. (2007) · Nature Genetics · doi:10.1038/ng2080 · Cited by 622 · see citing works
Sandesara, P. B., Virani, S. S., Fazio, S., & Shapiro, M. D. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00184 · Cited by 626 · see citing works
JBS3 Board (2014) · Heart · doi:10.1136/heartjnl-2014-305693 · Cited by 608 · see citing works
Recent Explosive Human Population Growth Has Resulted in an Excess of Rare Genetic Variants
Keinan, A., & Clark, A. G. (2012) · Science · doi:10.1126/science.1217283 · Cited by 548 · see citing works
Borén, J., & Williams, K. J. (2016) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000330 · Cited by 524 · see citing works
Anti-PCSK9 Antibody Effectively Lowers Cholesterol in Patients With Statin Intolerance
Stroes, E., Colquhoun, D., Sullivan, D., Civeira, F., Rosenson, R. S., Watts, G. F., Bruckert, E., Cho, L., Dent, R., Knusel, B., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.03.019 · Cited by 526 · see citing works
Permanent Alteration of PCSK9 With In Vivo CRISPR-Cas9 Genome Editing
Ding, Q., Strong, A., Patel, K. M., Ng, S.-L., Gosis, B. S., Regan, S. N., Cowan, C. A., Rader, D. J., & Musunuru, K. (2014) · Circulation Research · doi:10.1161/circresaha.115.304351 · Cited by 522 · see citing works
Translating molecular discoveries into new therapies for atherosclerosis
Rader, D. J., & Daugherty, A. (2008) · Nature · doi:10.1038/nature06796 · Cited by 515 · see citing works
Jørgensen, A. B., Frikke-Schmidt, R., West, A. S., Grande, P., Nordestgaard, B. G., & Tybjærg-Hansen, A. (2013) · European Heart Journal · doi:10.1093/eurheartj/ehs431 · Cited by 501 · see citing works
Coding Variation in <i>ANGPTL4,</i> <i>LPL,</i> and <i>SVEP1</i> and the Risk of Coronary Disease
Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia Investigators (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1507652 · Cited by 493 · see citing works
Hoogeveen, R. C., Gaubatz, J. W., Sun, W., Dodge, R. C., Crosby, J. R., Jiang, J., Couper, D., Virani, S. S., Kathiresan, S., Boerwinkle, E., et al. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303284 · Cited by 507 · see citing works
Self-citationDrug development in the era of precision medicine
Dugger, S. A., Platt, A., & Goldstein, D. B. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.226 · Cited by 493 · see citing works
Bjermo, H., Iggman, D., Kullberg, J., Dahlman, I., Johansson, L., Persson, L., Berglund, J., Pulkki, K., Basu, S., Uusitupa, M., et al. (2012) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.111.030114 · Cited by 490 · see citing works
Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer
Liu, X., Bao, X., Hu, M., Chang, H., Jiao, M., Cheng, J., Xie, L., Huang, Q., Li, F., & Li, C.-Y. (2020) · Nature · doi:10.1038/s41586-020-2911-7 · Cited by 490 · see citing works
ANGPTL3 deficiency and protection against coronary artery disease
Stitziel, N. O., Khera, A. V., Wang, X., Bierhals, A. J., Vourakis, A. C., Sperry, A. E., Natarajan, P., Klarin, D., Emdin, C. A., Zekavat, S. M., et al. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.02.030 · Cited by 467 · see citing works
Self-citationPlasma lipoproteins: genetic influences and clinical implications
Hegele, R. A. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2481 · Cited by 462 · see citing works
Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study
Mokry, L. E., Ross, S., Ahmad, O. S., Forgetta, V., Smith, G. D., Leong, A., Greenwood, C. M. T., Thanassoulis, G., & Richards, J. B. (2015) · PLOS Medicine · doi:10.1371/journal.pmed.1001866 · Cited by 445 · see citing works
Statistical analysis strategies for association studies involving rare variants
Bansal, V., Libiger, O., Torkamani, A., & Schork, N. J. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2867 · Cited by 455 · see citing works
Sullivan, D., Olsson, A. G., Scott, R., Kim, J. B., Xue, A., Gebski, V., Wasserman, S. M., & Stein, E. A. (2012) · JAMA · doi:10.1001/jama.2012.25790 · Cited by 447 · see citing works
Distinguishing genetic correlation from causation across 52 diseases and complex traits
O’Connor, L. J., & Price, A. L. (2018) · Nature Genetics · doi:10.1038/s41588-018-0255-0 · Cited by 394 · see citing works
Lotta, L. A., Scott, R. A., Sharp, S. J., Burgess, S., Luan, J., Tillin, T., Schmidt, A. F., Imamura, F., Stewart, I. D., Perry, J. R. B., et al. (2016) · PLOS Medicine · doi:10.1371/journal.pmed.1002179 · Cited by 417 · see citing works
Neil, A., Cooper, J., Betteridge, J., Capps, N., McDowell, I., Durrington, P., Seed, M., Humphries, S. E., & on behalf of the Simon Broome Familial Hyperlipidaemia Register Group (2008) · European Heart Journal · doi:10.1093/eurheartj/ehn422 · Cited by 425 · see citing works
Inactivating Mutations in <i>NPC1L1</i> and Protection from Coronary Heart Disease
The Myocardial Infarction Genetics Consortium Investigators (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1405386 · Cited by 419 · see citing works
Schwartz, G. G., Bessac, L., Berdan, L. G., Bhatt, D. L., Bittner, V., Diaz, R., Goodman, S. G., Hanotin, C., Harrington, R. A., Jukema, J. W., et al. (2014) · American Heart Journal · doi:10.1016/j.ahj.2014.07.028 · Cited by 408 · see citing works
The impact of low-frequency and rare variants on lipid levels
ENGAGE Consortium, Surakka, I., Horikoshi, M., Mägi, R., Sarin, A.-P., Mahajan, A., Lagou, V., Marullo, L., Ferreira, T., Miraglio, B., et al. (2015) · Nature Genetics · doi:10.1038/ng.3300 · Cited by 351 · see citing works
PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study
Schmidt, A. F., Swerdlow, D. I., Holmes, M. V., Patel, R. S., Fairhurst-Hunter, Z., Lyall, D. M., Hartwig, F. P., Horta, B. L., Hyppönen, E., Power, C., et al. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(16)30396-5 · Cited by 380 · see citing works
Diversity and inclusion in genomic research: why the uneven progress?
Bentley, A. R., Callier, S., & Rotimi, C. N. (2017) · Journal of Community Genetics · doi:10.1007/s12687-017-0316-6 · Cited by 357 · see citing works
Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study
Kaplan, H., Thompson, R. C., Trumble, B. C., Wann, L. S., Allam, A. H., Beheim, B., Frohlich, B., Sutherland, M. L., Sutherland, J. D., Stieglitz, J., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30752-3 · Cited by 338 · see citing works
Using Mendelian Randomization to Improve the Design of Randomized Trials
Ference, B. A., Holmes, M. V., & Smith, G. D. (2021) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a040980 · Cited by 338 · see citing works
Effect of predicted protein-truncating genetic variants on the human transcriptome
Rivas, M. A., Pirinen, M., Conrad, D. F., Lek, M., Tsang, E. K., Karczewski, K. J., Maller, J. B., Kukurba, K. R., DeLuca, D. S., Fromer, M., et al. (2015) · Science · doi:10.1126/science.1261877 · Cited by 313 · see citing works
Wadhera, R. K., Steen, D. L., Khan, I., Giugliano, R. P., & Foody, J. M. (2016) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2015.11.010 · Cited by 306 · see citing works
Akbari, P., Gilani, A., Sosina, O., Kosmicki, J. A., Khrimian, L., Fang, Y.-Y., Persaud, T., Garcia, V., Sun, D., Li, A., et al. (2021) · Science · doi:10.1126/science.abf8683 · Cited by 276 · see citing works
LDL cholesterol: controversies and future therapeutic directions
Ridker, P. M. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61009-6 · Cited by 274 · see citing works
The Evolving Future of PCSK9 Inhibitors
Rosenson, R. S., Hegele, R. A., Fazio, S., & Cannon, C. P. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.04.054 · Cited by 264 · see citing works
Lange, L. A., Carlson, C. S., Hindorff, L. A., Lange, E. M., Walston, J., Durda, J. P., Cushman, M., Bis, J. C., Zeng, D., Lin, D., et al. (2006) · JAMA · doi:10.1001/jama.296.22.2703 · Cited by 266 · see citing works
Safety and efficacy of anti-PCSK9 antibodies: a meta-analysis of 25 randomized, controlled trials
Zhang, X.-L., Zhu, Q.-Q., Zhu, L., Chen, J.-Z., Chen, Q.-H., Li, G.-N., Xie, J., Kang, L.-N., & Xu, B. (2015) · BMC Medicine · doi:10.1186/s12916-015-0358-8 · Cited by 260 · see citing works
Lipinski, M. J., Benedetto, U., Escarcega, R. O., Biondi-Zoccai, G., Lhermusier, T., Baker, N. C., Torguson, R., Brewer, H. B., & Waksman, R. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehv563 · Cited by 256 · see citing works
Naude, C. E., Schoonees, A., Senekal, M., Young, T., Garner, P., & Volmink, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100652 · Cited by 252 · see citing works
2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia
Blumenthal, R. S., Morris, P. B., Gaudino, M., Johnson, H. M., Anderson, T. S., Bittner, V. A., Blankstein, R., Brewer, L. C., Cho, L., de Ferranti, S. D., et al. (2026) · JACC · doi:10.1016/j.jacc.2025.11.016 · Cited by 304 · see citing works
From Lipids to Inflammation: New Approaches to Reducing Atherosclerotic Risk
Shapiro, M. D., & Fazio, S. (2016) · Circulation Research · doi:10.1161/circresaha.115.306471 · Cited by 217 · see citing works
Karatasakis, A., Danek, B. A., Karacsonyi, J., Rangan, B. V., Roesle, M. K., Knickelbine, T., Miedema, M. D., Khalili, H., Ahmad, Z., Abdullah, S., et al. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.006910 · Cited by 215 · see citing works
Da Dalt, L., Ruscica, M., Bonacina, F., Balzarotti, G., Dhyani, A., Di Cairano, E., Baragetti, A., Arnaboldi, L., De Metrio, S., Pellegatta, F., et al. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehy357 · Cited by 209 · see citing works
Lowering LDL—not only how low, but how long?
Brown, M. S., & Goldstein, J. L. (2006) · Science · doi:10.1126/science.1125884 · Cited by 204 · see citing works
Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion
Wang, Y., Gusarova, V., Banfi, S., Gromada, J., Cohen, J. C., & Hobbs, H. H. (2015) · Journal of Lipid Research · doi:10.1194/jlr.m054882 · Cited by 189 · see citing works
Self-citationWang, N., Fulcher, J., Abeysuriya, N., Park, L., Kumar, S., Di Tanna, G. L., Wilcox, I., Keech, A., Rodgers, A., & Lal, S. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30388-2 · Cited by 187 · see citing works
- Authors
- Cohen, J. C., Boerwinkle, E., Mosley, T. H., & Hobbs, H. H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- The University of Texas Health Science Center at Houston (US)
- Howard Hughes Medical Institute (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2006-03-23
- Volume
- 354
- Issue
- 12
- Pages
- 1264-1272
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2067539811
- Semantic Scholar
- 5cb1ad66116f87a0743739413b3b5f7f633657f8
- Cited by
- 3,181
- References
- 28
- Citations by year
- 2026: 130 · 2025: 121 · 2024: 150 · 2023: 182 · 2022: 169 · 2021: 175 · 2020: 193 · 2019: 180 · 2018: 210 · 2017: 229 · 2016: 235 · 2015: 244 · 2014: 171 · 2013: 145 · 2012: 126
- FWCI
- 104.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- W. M. Keck Foundation
- Donald W. Reynolds Foundation
- National Institutes of Health (n01hc55021-47-0-1, n01hc55020-39-0-0, n01hc55016-37-0-0, n01hc055022-024, n01hc55019-35-0-1, n01hc55018-38-0-1, N01-HC55020, N01-HC-55021, HL20948, N01-HC-55019, N01-HC-55022, N01-HC55016, N01-HC55018, N01-HC-55015, n01hc55015-48-0-1)
- National Heart, Lung, and Blood Institute (N01-HC55022, N01-HC-55018, HL-20948, N01 HC 55020, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022, N01 HC 55019, N01-HC55016, P01HL020948, N01‐HC‐55015, N01-HC55021)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- PCSK9, LDL cholesterol, coronary artery disease, myocardial infarction, coronary revascularization, nonsense mutation, genetic variants, LDL cholesterol lowering, cardiovascular risk, Atherosclerosis Risk in Communities Study, black and white populations
- MeSH terms
- Proprotein Convertase 9, Black or African American, Carotid Arteries, Coronary Disease, Female, Gene Frequency, Genotype, Humans, Hypolipoproteinemias, Cholesterol, LDL, Male, Middle Aged, Risk, Serine Endopeptidases, United States, Genetic Variation, Cohort Studies, Incidence, Proportional Hazards Models, Codon, Nonsense, Proprotein Convertases, Black People, White People
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