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Science 6 August 2004:
Vol. 305. no. 5685, pp. 869 - 872
DOI: 10.1126/science.1099870
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Reports

Multiple Rare Alleles Contribute to Low Plasma Levels of HDL Cholesterol

Jonathan C. Cohen,1,2,3*{dagger} Robert S. Kiss,5* Alexander Pertsemlidis,1 Yves L. Marcel,5{dagger} Ruth McPherson,5 Helen H. Hobbs1,3,4

Heritable variation in complex traits is generally considered to be conferred by common DNA sequence polymorphisms. We tested whether rare DNA sequence variants collectively contribute to variation in plasma levels of highdensity lipoprotein cholesterol (HDL-C). We sequenced three candidate genes (ABCA1, APOA1, and LCAT) that cause Mendelian forms of low HDL-C levels in individuals from a population-based study. Nonsynonymous sequence variants were significantly more common (16% versus 2%) in individuals with low HDL-C (<fifth percentile) than in those with high HDL-C (>95th percentile). Similar findings were obtained in an independent population, and biochemical studies indicated that most sequence variants in the low HDL-C group were functionally important. Thus, rare alleles with major phenotypic effects contribute significantly to low plasma HDL-C levels in the general population.

1 Donald W. Reynolds Cardiovascular Clinical Research Center and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
2 Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
3 Department of Internal Medicine and Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
4 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
5 Lipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, Ottawa, Ontario K7Y4W7, Canada.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: jonathan.cohen{at}utsouthwestern.edu (J.C.C.); ymarcel{at}ottawaheart.ca (Y.L.M.)

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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B. Haidar, R. S. Kiss, L. Sarov-Blat, R. Brunet, C. Harder, R. McPherson, and Y. L. Marcel (2006)
J. Biol. Chem. 281, 39971-39981
   Abstract »    Full Text »    PDF »
Overrepresentation of rare variants in a specific ethnic group may confuse interpretation of association analyses.
D. Keen-Kim, C. A. Mathews, V. I. Reus, T. L. Lowe, L. D. Herrera, C. L. Budman, V. Gross-Tsur, A. E. Pulver, R. D. Bruun, G. Erenberg, et al. (2006)
Hum. Mol. Genet. 15, 3324-3328
   Abstract »    Full Text »    PDF »
ATP-Binding Cassette Cholesterol Transporters and Cardiovascular Disease.
J. F. Oram and A. M. Vaughan (2006)
Circ. Res. 99, 1031-1043
   Abstract »    Full Text »    PDF »
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J. C. Cohen (2006)
J. Am. Coll. Cardiol. 48, A10-A14
   Abstract »    Full Text »    PDF »
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E. J. Topol, J. Smith, E. F. Plow, and Q. K. Wang (2006)
Hum. Mol. Genet. 15, R117-R123
   Abstract »    Full Text »    PDF »
Mechanisms for cellular cholesterol transport: defects and human disease..
E. Ikonen (2006)
Physiol Rev 86, 1237-1261
   Abstract »    Full Text »    PDF »
High-throughput discovery of rare human nucleotide polymorphisms by Ecotilling.
B. J. Till, T. Zerr, E. Bowers, E. A. Greene, L. Comai, and S. Henikoff (2006)
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   Abstract »    Full Text »    PDF »
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H. Wittenburg, M. A. Lyons, R. Li, U. Kurtz, X. Wang, J. Mossner, G. A. Churchill, M. C. Carey, and B. Paigen (2006)
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   Abstract »    Full Text »    PDF »
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E. K. Silverman (2006)
Proceedings of the ATS 3, 405-408
   Abstract »    Full Text »    PDF »
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R. C Millikan (2006)
Int. J. Epidemiol. 35, 578-581
   Full Text »    PDF »
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A. Eyre-Walker, M. Woolfit, and T. Phelps (2006)
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   Abstract »    Full Text »    PDF »
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M. L. Maitland, A. DiRienzo, and M. J. Ratain (2006)
J. Clin. Oncol. 24, 2151-2157
   Abstract »    Full Text »    PDF »
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M. C. Stene, R. Frikke-Schmidt, B. G. Nordestgaard, and A. Tybjaerg-Hansen (2006)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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K. Inoue, Y. Mineharu, S. Inoue, S. Yamada, F. Matsuda, K. Nozaki, K. Takenaka, N. Hashimoto, and A. Koizumi (2006)
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   Abstract »    Full Text »    PDF »
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L. Peltonen, M. Perola, J. Naukkarinen, and A. Palotie (2006)
Hum. Mol. Genet. 15, R67-R74
   Full Text »    PDF »
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S. Kathiresan, M. G. Larson, R. S. Vasan, C.-Y. Guo, P. Gona, J. F. Keaney Jr, P. W.F. Wilson, C. Newton-Cheh, S. L. Musone, A. L. Camargo, et al. (2006)
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   Abstract »    Full Text »    PDF »
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B. F. Pachkowski, S. Winkel, Y. Kubota, J. A. Swenberg, R. C. Millikan, and J. Nakamura (2006)
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   Abstract »    Full Text »    PDF »
Genetic variation in bactericidal/permeability-increasing protein influences the risk of developing rapid airflow decline after hematopoietic cell transplantation.
J. W. Chien, L. P. Zhao, J. A. Hansen, W. H. Fan, T. Parimon, and J. G. Clark (2006)
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   Abstract »    Full Text »    PDF »
Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels.
J. C. Cohen, A. Pertsemlidis, S. Fahmi, S. Esmail, G. L. Vega, S. M. Grundy, and H. H. Hobbs (2006)
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   Abstract »    Full Text »    PDF »
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T. J. Urban, R. Sebro, E. H. Hurowitz, M. K. Leabman, I. Badagnani, L. L. Lagpacan, N. Risch, and K. M. Giacomini (2006)
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   Abstract »    Full Text »    PDF »
Evidence for a Gene Influencing High-Density Lipoprotein Cholesterol on Chromosome 4q31.21.
Z. Dastani, L. Quiogue, C. Plaisier, J. C. Engert, M. Marcil, J. Genest, and P. Pajukanta (2006)
Arterioscler Thromb Vasc Biol 26, 392-397
   Abstract »    Full Text »    PDF »
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K.-i. Okuhira, M. L. Fitzgerald, D. A. Sarracino, J. J. Manning, S. A. Bell, J. L. Goss, and M. W. Freeman (2005)
J. Biol. Chem. 280, 39653-39664
   Abstract »    Full Text »    PDF »
Determinants of the success of whole-genome association testing.
A. G. Clark, E. Boerwinkle, J. Hixson, and C. F. Sing (2005)
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   Full Text »    PDF »
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Y. Kukita, K. Miyatake, R. Stokowski, D. Hinds, K. Higasa, N. Wake, T. Hirakawa, H. Kato, T. Matsuda, K. Pant, et al. (2005)
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   Abstract »    Full Text »    PDF »
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R. Frikke-Schmidt, B. G. Nordestgaard, P. Schnohr, R. Steffensen, and A. Tybjaerg-Hansen (2005)
J. Am. Coll. Cardiol. 46, 1516-1520
   Abstract »    Full Text »    PDF »
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M. Faham, J. Zheng, M. Moorhead, H. Fakhrai-Rad, E. Namsaraev, K. Wong, Z. Wang, S. G. Chow, L. Lee, K. Suyenaga, et al. (2005)
PNAS 102, 14717-14722
   Abstract »    Full Text »    PDF »
ATP-Binding Cassette Transporter A1: A Cell Cholesterol Exporter That Protects Against Cardiovascular Disease.
J. F. Oram and J. W. Heinecke (2005)
Physiol Rev 85, 1343-1372
   Abstract »    Full Text »    PDF »
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M. Fornage, C. R. Lee, P. A. Doris, M. S. Bray, G. Heiss, D. C. Zeldin, and E. Boerwinkle (2005)
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   Abstract »    Full Text »    PDF »
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C. M. Kelleher, E. K. Silverman, T. Broekelmann, A. A. Litonjua, M. Hernandez, J. S. Sylvia, J. Stoler, J. J. Reilly, H. A. Chapman, F. E. Speizer, et al. (2005)
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   Abstract »    Full Text »    PDF »
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A. E. Guttmacher and F. S. Collins (2005)
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   Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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R. S. Kiss, J. Maric, and Y. L. Marcel (2005)
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   Abstract »    Full Text »    PDF »
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M. M. Wurfel, W. Y. Park, F. Radella, J. Ruzinski, A. Sandstrom, J. Strout, R. E. Bumgarner, and T. R. Martin (2005)
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Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome).
P J Ferguson, S Chen, M K Tayeh, L Ochoa, S M Leal, A Pelet, A Munnich, S Lyonnet, H A Majeed, and H El-Shanti (2005)
J. Med. Genet. 42, 551-557
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New Insights Into the Regulation of HDL Metabolism and Reverse Cholesterol Transport.
G. F. Lewis and D. J. Rader (2005)
Circ. Res. 96, 1221-1232
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A rare variant of the leptin gene has large effects on blood pressure and carotid intima-medial thickness: a study of 1428 individuals in 248 families.
N Gaukrodger, B M Mayosi, H Imrie, P Avery, M Baker, J M C Connell, H Watkins, M Farrall, and B Keavney (2005)
J. Med. Genet. 42, 474-478
   Abstract »    Full Text »    PDF »
Automated band mapping in electrophoretic gel images using background information.
T. Zerr and S. Henikoff (2005)
Nucleic Acids Res. 33, 2806-2812
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Denaturing high-performance liquid chromatography in the detection of ABCA1 gene mutations in familial HDL deficiency.
T. Fasano, L. Bocchi, L. Pisciotta, S. Bertolini, and S. Calandra (2005)
J. Lipid Res. 46, 817-822
   Abstract »    Full Text »    PDF »
Cardiovascular Genomics and Oxidative Stress.
A. F. Dominiczak, D. Graham, M. W. McBride, N. J.R. Brain, W. K. Lee, F. J. Charchar, M. Tomaszewski, C. Delles, and C. A. Hamilton (2005)
Hypertension 45, 636-642
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Haplotypes produced from rare variants in the promoter and coding regions of angiotensinogen contribute to variation in angiotensinogen levels.
X. Zhu, L. Fejerman, A. Luke, A. Adeyemo, and R. S. Cooper (2005)
Hum. Mol. Genet. 14, 639-643
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