A Spectrum of PCSK9 Alleles Contributes to Plasma Levels of Low-Density Lipoprotein Cholesterol
Open accessAbstract
Selected missense mutations in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) cause autosomal dominant hypercholesterolemia, whereas nonsense mutations in the same gene are associated with low plasma levels of low-density lipoprotein cholesterol (LDL-C). Here, DNA sequencing and chip-based oligonucleotide hybridization were used to determine whether other sequence variations in PCSK9 contribute to differences in LDL-C levels. The coding regions of PCSK9 were sequenced in the blacks and whites from the Dallas Heart Study (n=3,543) who had the lowest (<5th percentile) and highest (>95th percentile) plasma levels of LDL-C. Of the 17 missense variants identified, 3 (R46L, L253F, and A443T) were significantly and reproducibly associated with lower plasma levels of LDL-C (reductions ranging from 3.5% to 30%). None of the low-LDL-C variants were associated with increased hepatic triglyceride content, as measured by proton magnetic resonance spectroscopy. This finding is most consistent with the reduction in LDL-C being caused primarily by accelerating LDL clearance, rather than by reduced lipoprotein production. Association studies with 93 noncoding single-nucleotide polymorphisms (SNPs) at the PCSK9 locus identified 3 SNPs associated with modest differences in plasma LDL-C levels. Thus, a spectrum of sequence variations ranging in frequency (from 0.2% to 34%) and magnitude of effect (from a 3% increase to a 49% decrease) contribute to interindividual differences in LDL-C levels. These findings reveal that PCSK9 activity is a major determinant of plasma levels of LDL-C in humans and make it an attractive therapeutic target for LDL-C lowering.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The gene encoding PCSK9 contains very rare mutations causing autosomal dominant hypercholesterolemia and high-frequency common variants with modest effects.
“The gene encoding PCSK9 contains very rare mutations causing autosomal dominant hypercholesterolemia (discovered by linkage analysis), as well as high-frequency common variants with modest effects.”
From Genetic Mapping in Human Disease (2008) · cites this paper as [126]
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 [126]
Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,706 · see citing works
Haploview: analysis and visualization of LD and haplotype maps
Barrett, J., Fry, B., Maller, J., & Daly, M. (2005) · Bioinform. · doi:10.1093/bioinformatics/bth457 · Cited by 15,086 · see citing works
The Metabolic and Molecular Bases of Inherited Disease
Scriver, R. C. (1995) · Medical Entomology and Zoology · Cited by 12,101 · see citing works
SIFT: predicting amino acid changes that affect protein function
Ng, P. C. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg509 · Cited by 6,601 · see citing works
The Structure of Haplotype Blocks in the Human Genome
Gabriel, S. B., Schaffner, S. F., Nguyen, H., Moore, J. M., Roy, J., Blumenstiel, B., Higgins, J., DeFelice, M., Lochner, A., Faggart, M., et al. (2002) · Science · doi:10.1126/science.1069424 · Cited by 5,863 · see citing works
Self-citationPrevalence of Hepatic Steatosis in An Urban Population in the United States: Impact of Ethnicity
Browning, J. D., Szczepaniak, L. S., Dobbins, R., Nuremberg, P., Horton, J. D., Cohen, J. C., Grundy, S. M., & Hobbs, H. H. (2004) · Hepatology · doi:10.1002/hep.20466 · Cited by 3,664 · see citing works
Self-citationMutations in PCSK9 cause autosomal dominant hypercholesterolemia
Abifadel, M., Varret, M., Rabès, J.-P., Allard, D., Ouguerram, K., Devillers, M., Cruaud, C., Benjannet, S., Wickham, L., Erlich, D., et al. (2003) · Nature Genetics · doi:10.1038/ng1161 · Cited by 2,985 · see citing works
Szczepaniak, L. S., Nurenberg, P., Leonard, D. S., Browning, J. D., Reingold, J. S., Grundy, S. M., Hobbs, H. H., & Dobbins, R. L. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00064.2004 · Cited by 1,562 · see citing works
Self-citationHorton, J. D., Shah, N. A., Warrington, J. A., Anderson, N. N., Park, S. W., Brown, M. S., & Goldstein, J. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1534923100 · Cited by 1,427 · 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
Prediction of deleterious human alleles
Sunyaev, S. R. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.6.591 · Cited by 1,042 · 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
Thomas, P. D. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg115 · Cited by 660 · 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
Garcia, C. K., Wilund, K., Arca, M., Zuliani, G., Fellin, R., Maioli, M., Calandra, S., Bertolini, S., Cossu, F., Grishin, N., et al. (2001) · Science · doi:10.1126/science.1060458 · Cited by 624 · see citing works
Self-citationDubuc, 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
Victor, R. G., Haley, R. W., Willett, D. L., Peshock, R. M., Vaeth, P. C., Leonard, D. S., Basit, M. A., Cooper, R., Iannacchione, V. G., Visscher, W. A., et al. (2004) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2004.02.058 · Cited by 526 · see citing works
Self-citationSacks, F., & Katan, M. (2002) · American Journal of Medicine · doi:10.1016/s0002-9343(01)00987-1 · Cited by 523 · see citing works
Park, S. W., Moon, Y.-A., & Horton, J. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410077200 · Cited by 500 · see citing works
AVID: A Global Alignment ProgramPreprint
Bray, N., Dubchak, I. L., & Pachter, L. S. (2002) · Genome Research · doi:10.1101/gr.789803 · Cited by 495 · see citing works
Innerarity, T. L., Mahley, R. W., Weisgraber, K. H., Bersot, T. P., Krauss, R. M., Vega, G., Grundy, S. M., Friedl, W., Davignon, J., & McCarthy, B. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42605-7 · Cited by 446 · see citing works
Self-citationGenetic and Environmental Influences on Serum Lipid Levels in Twins
Heller, D. A., Fairé, U. D., Pedersen, N. L., Dahlén, G. H., & McClearn, G. E. (1993) · New England Journal of Medicine · doi:10.1056/nejm199304223281603 · Cited by 440 · see citing works
Maxwell, K. N., Soccio, R. E., Duncan, E. M., Sehayek, E., & Breslow, J. L. (2003) · Journal of Lipid Research · doi:10.1194/jlr.m300203-jlr200 · Cited by 374 · see citing works
A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree
Timms, K. M., Wagner, S., Samuels, M. E., Forbey, K. C., Goldfine, H., Jammulapati, S., Skolnick, M. H., Hopkins, P. N., Hunt, S. C., & Shattuck, D. (2004) · Human Genetics · doi:10.1007/s00439-003-1071-9 · Cited by 322 · see citing works
Dobzhansky–Muller incompatibilities in protein evolution
Kondrashov, A. S., Sunyaev, S. R., & Kondrashov, F. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.232565499 · Cited by 306 · see citing works
Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia
Leren, T. (2004) · Clinical Genetics · doi:10.1111/j.0009-9163.2004.0238.x · Cited by 256 · see citing works
Strategies and tools for whole-genome alignments
Couronne, O., Poliakov, A., Bray, N., Ishkhanov, T., Ryaboy, D., Rubin, E., Pachter, L., & Dubchak, I. (2003) · Genome Research · doi:10.1101/gr.762503 · Cited by 224 · see citing works
Ouguerram, K., Chétiveaux, M., Zaïr, Y., Costet, P., Abifadel, M., Varret, M., Boileau, C., Magot, T., & Krempf, M. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000133684.77013.88 · Cited by 184 · see citing works
Chen, S. N., Ballantyne, C. M., Gotto, A. M., Tan, Y., Willerson, J. T., & Marian, A. J. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.01.051 · Cited by 162 · see citing works
Functional characterization of Narc 1, a novel proteinase related to proteinase K
Naureckiene, S., Ma, L., Sreekumar, K. R., Purandare, U., Lo, C. F., Huang, Y., Chiang, L. W., Grenier, J. M., Ozenberger, B. A., Jacobsen, J. S., et al. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.09.011 · Cited by 153 · see citing works
Brown, M. S., & Goldstein, J. L. (2001) · Encyclopedia of Genetics · doi:10.1006/rwgn.2001.0444 · Cited by 152 · see citing works
Sun, X.-M., Eden, E. R., Tosi, I., Neuwirth, C. K. Y., Wile, D. B., Naoumova, R. P., & Soutar, A. K. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi128 · Cited by 150 · see citing works
Schonfeld, G., Patterson, B. W., Yablonskiy, D. A., Tanoli, T. S. K., Averna, M. R., Elias, N., Yue, P., & Ackerman, J. J. H. (2003) · Journal of Lipid Research · doi:10.1194/jlr.m200342-jlr200 · Cited by 143 · see citing works
Rao, D. C., Laskarzewski, P. M., Morrison, J. A., et al. (1982) · PubMed · Cited by 133 · 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
Genetic variants in PCSK9 affect the cholesterol level in Japanese
Shioji, K., Mannami, T., Kokubo, Y., Inamoto, N., Takagi, S., Goto, Y., Nonogi, H., & Iwai, N. (2004) · Journal of Human Genetics · doi:10.1007/s10038-003-0114-3 · Cited by 82 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Finding the missing heritability of complex diseases
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., et al. (2009) · Nature · doi:10.1038/nature08494 · Cited by 8,336 · see citing works
Sequence Variations in <i>PCSK9,</i> Low LDL, and Protection against Coronary Heart Disease
Cohen, J. C., Boerwinkle, E., Mosley, T. H., & Hobbs, H. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054013 · Cited by 3,181 · see citing works
Self-citationGenome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
Saxena, R., Voight, B. F., Lyssenko, V., Burtt, N. P., de Bakker, P. I. W., Chen, H., Roix, J. J., Kathiresan, S., Hirschhorn, J. N., Daly, M. J., et al. (2007) · Science · doi:10.1126/science.1142358 · Cited by 2,843 · 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
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
Human genetic variation and its contribution to complex traits
Frazer, K. A., Murray, S. S., Schork, N. J., & Topol, E. J. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2554 · Cited by 1,073 · see citing works
Inclisiran 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
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
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
An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people
Nelson, M. R., Wegmann, D., Ehm, M. G., Kessner, D., St. Jean, P., Verzilli, C., Shen, J., Tang, Z., Bacanu, S.-A., Fraser, D., et al. (2012) · Science · doi:10.1126/science.1217876 · Cited by 647 · 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
Romeo, S., Pennacchio, L. A., Fu, Y., Boerwinkle, E., Tybjaerg-Hansen, A., Hobbs, H. H., & Cohen, J. C. (2007) · Nature Genetics · doi:10.1038/ng1984 · Cited by 511 · 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
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
Exome sequencing and the genetic basis of complex traits
Kiezun, A., Garimella, K., Do, R., Stitziel, N. O., Neale, B. M., McLaren, P. J., Gupta, N., Sklar, P., Sullivan, P. F., Moran, J. L., et al. (2012) · Nature Genetics · doi:10.1038/ng.2303 · Cited by 372 · see citing works
Shifting Paradigm of Association Studies: Value of Rare Single-Nucleotide Polymorphisms
Gorlov, I. P., Gorlova, O. Y., Sunyaev, S. R., Spitz, M. R., & Amos, C. I. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.09.006 · Cited by 338 · see citing works
A Data-Adaptive Sum Test for Disease Association with Multiple Common or Rare Variants
Han, F., & Pan, W. (2010) · Human Heredity · doi:10.1159/000288704 · Cited by 306 · 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
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
Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): From bench to bedside
Bao, X., Liang, Y., Chang, H., Cai, T., Feng, B., Gordon, K., Zhu, Y., Shi, H., He, Y., & Xie, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01690-3 · Cited by 187 · see citing works
Guilt beyond a reasonable doubt
Altshuler, D., & Daly, M. (2007) · Nature Genetics · doi:10.1038/ng0707-813 · Cited by 151 · see citing works
Benn, M. (2009) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2009.01.004 · Cited by 119 · see citing works
Ni, Y. G., Condra, J. H., Orsatti, L., Shen, X., Di Marco, S., Pandit, S., Bottomley, M. J., Ruggeri, L., Cummings, R. T., Cubbon, R. M., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.113035 · Cited by 107 · see citing works
Rousselet, E., Marcinkiewicz, J., Kriz, J., Zhou, A., Hatten, M. E., Prat, A., & Seidah, N. G. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m014118 · Cited by 107 · see citing works
Abboud, S., Karhunen, P. J., Lütjohann, D., Goebeler, S., Luoto, T., Friedrichs, S., Lehtimaki, T., Pandolfo, M., & Laaksonen, R. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001043 · Cited by 77 · see citing works
Gibbs, J. P., Doshi, S., Kuchimanchi, M., Grover, A., Emery, M. G., Dodds, M. G., Gibbs, M. A., Somaratne, R., Wasserman, S. M., & Blom, D. (2017) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.840 · Cited by 42 · see citing works
New Approaches for Targeting PCSK9: Small-Interfering Ribonucleic Acid and Genome Editing
Oostveen, R. F., Khera, A. V., Kathiresan, S., Stroes, E. S. G., Fitzgerald, K., Harms, M. J., Oakes, B. L., & Kastelein, J. J. P. (2023) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.122.317963 · Cited by 31 · see citing works
Radwan, Z. H., Wang, X., Waqar, F., Pirim, D., Niemsiri, V., Hokanson, J. E., Hamman, R. F., Bunker, C. H., Barmada, M. M., Demirci, F. Y., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114618 · Cited by 27 · see citing works
Aherrahrou, R., Reinberger, T., Hashmi, S., & Erdmann, J. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae161 · Cited by 25 · see citing works
Alirocumab: PCSK9 inhibitor for LDL cholesterol reduction
Tavori, H., Melone, M., & Rashid, S. (2014) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.2014.954551 · Cited by 21 · see citing works
DNA Sequence‐Based Phenotypic Association Analysis
Schork, N. J., Wessel, J., & Malo, N. (2008) · Advances in Genetics · doi:10.1016/s0065-2660(07)00409-9 · Cited by 22 · see citing works
PCSK9 Mediates Dyslipidemia Induced by Olanzapine Treatment in Schizophrenia Patients
Huang, J., Xiao, J., Peng, Z., Shao, P., Sun, M., Long, Y., Wang, X., Shen, M., Kang, D., Yang, Y., et al. (2022) · Psychopharmacology · doi:10.1007/s00213-021-06042-z · Cited by 16 · see citing works
- Authors
- Kotowski, I. K., Pertsemlidis, A., Luke, A., Cooper, R. S., Vega, G. L., Cohen, J. C., & Hobbs, H. H.
- Affiliations
- Howard Hughes Medical Institute (US)
- Loyola University Medical Center (US)
- Corresponding author
- Hobbs, Helen H.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 78
- Issue
- 3
- Pages
- 410-422
- ISSN
- 0002-9297 (ISSN-L)
- OpenAlex
- W2110124859
- Cited by
- 517
- References
- 38
- Citations by year
- 2026: 13 · 2025: 8 · 2024: 10 · 2023: 13 · 2022: 15 · 2021: 18 · 2020: 19 · 2019: 30 · 2018: 26 · 2017: 24 · 2016: 23 · 2015: 34 · 2014: 35 · 2013: 22 · 2012: 26
- FWCI
- 44.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- Civil War Book Review (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Donald W. Reynolds Foundation
- National Heart, Lung, and Blood Institute (HL-20948, P01HL020948)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- PCSK9, LDL cholesterol, missense mutations, LDL cholesterol lowering, autosomal dominant hypercholesterolemia, LDL clearance, hepatic triglyceride content, single nucleotide polymorphisms, genetic variants, Dallas Heart Study, LDL-C lowering therapy
- MeSH terms
- Proprotein Convertase 9, Alleles, Amino Acid Sequence, Female, Gene Frequency, Haplotypes, Humans, Hypercholesterolemia, Cholesterol, LDL, Male, Molecular Sequence Data, Mutation, Serine Endopeptidases, Evolution, Molecular, Polymorphism, Single Nucleotide, Proprotein Convertases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
