Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Whatman Inc.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Originally published in Science Express on 3 May 2007
Science 8 June 2007:
Vol. 316. no. 5830, pp. 1488 - 1491
DOI: 10.1126/science.1142447
Prev | Table of Contents | Next

Reports

A Common Allele on Chromosome 9 Associated with Coronary Heart Disease

Ruth McPherson,1*{dagger} Alexander Pertsemlidis,2* Nihan Kavaslar,1 Alexandre Stewart,1 Robert Roberts,1 David R. Cox,3 David A. Hinds,3 Len A. Pennacchio,4,5 Anne Tybjaerg-Hansen,6 Aaron R. Folsom,7 Eric Boerwinkle,8 Helen H. Hobbs,2,9 Jonathan C. Cohen2,10{dagger}

Coronary heart disease (CHD) is a major cause of death in Western countries. We used genome-wide association scanning to identify a 58-kilobase interval on chromosome 9p21 that was consistently associated with CHD in six independent samples (more than 23,000 participants) from four Caucasian populations. This interval, which is located near the CDKN2A and CDKN2B genes, contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension, or diabetes. Homozygotes for the risk allele make up 20 to 25% of Caucasians and have a ~30 to 40% increased risk of CHD.

1 Division of Cardiology, University of Ottawa Heart Institute, Ottawa K1Y4W7, Canada.
2 Donald W. Reynolds Cardiovascular Clinical Research Center and the Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
3 Perlegen Sciences, Mountain View, CA 94043, USA.
4 Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
5 U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.
6 Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen DK-2100, Denmark.
7 Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55454, USA.
8 Human Genetics Center and Institute for Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA.
9 Howard Hughes Medical Institute at the University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
10 Center for Human Nutrition at the University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

* These authors contributed equally to this work.

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets.
B. S. Sutton, D. R. Crosslin, S. H. Shah, S. C. Nelson, A. Bassil, A. B. Hale, C. Haynes, P. J. Goldschmidt-Clermont, J. M. Vance, D. Seo, et al. (2008)
Hum. Mol. Genet. 17, 1318-1328
   Abstract »    Full Text »    PDF »
Whole Genome Analyses Suggest Ischemic Stroke and Heart Disease Share an Association With Polymorphisms on Chromosome 9p21.
M. Matarin, W. M. Brown, A. Singleton, J. A. Hardy, J. F. Meschia, and for the ISGS investigators (2008)
Stroke 39, 1586-1589
   Abstract »    Full Text »    PDF »
Genomics in cardiac metabolism.
J.-L. Samuel, M. C. Schaub, M. Zaugg, M. Mamas, W. B. Dunn, and B. Swynghedauw (2008)
Cardiovasc Res
   Abstract »    Full Text »    PDF »
No Significant Association of 14 Candidate Genes With Schizophrenia in a Large European Ancestry Sample: Implications for Psychiatric Genetics.
A. R. Sanders, J. Duan, D. F. Levinson, J. Shi, D. He, C. Hou, G. J. Burrell, J. P. Rice, D. A. Nertney, A. Olincy, et al. (2008)
Am J Psychiatry 165, 497-506
   Abstract »    Full Text »    PDF »
A survey of allelic imbalance in F1 mice.
C. D. Campbell, A. Kirby, J. Nemesh, M. J. Daly, and J. N. Hirschhorn (2008)
Genome Res. 18, 555-563
   Abstract »    Full Text »    PDF »
Angiotensin II Type 1 Receptor 1166C Polymorphism Is Associated With Abdominal Aortic Aneurysm in Three Independent Cohorts.
G. T. Jones, A. R. Thompson, F. M. van Bockxmeer, H. Hafez, J. A. Cooper, J. Golledge, S. E. Humphries, P. E. Norman, and A. M. van Rij (2008)
Arterioscler. Thromb. Vasc. Biol. 28, 764-770
   Abstract »    Full Text »    PDF »
Where Do We Go for Atherothrombotic Disease Genetics?.
S.-M. Brand-Herrmann (2008)
Stroke 39, 1070-1075
   Full Text »    PDF »
Repeated Replication and a Prospective Meta-Analysis of the Association Between Chromosome 9p21.3 and Coronary Artery Disease.
H. Schunkert, A. Gotz, P. Braund, R. McGinnis, D.-A. Tregouet, M. Mangino, P. Linsel-Nitschke, F. Cambien, C. Hengstenberg, K. Stark, et al. (2008)
Circulation 117, 1675-1684
   Abstract »    Full Text »    PDF »
Polymorphisms Associated with Cholesterol and Risk of Cardiovascular Events.
S. Kathiresan, O. Melander, D. Anevski, C. Guiducci, N. P. Burtt, C. Roos, J. N. Hirschhorn, G. Berglund, B. Hedblad, L. Groop, et al. (2008)
N. Engl. J. Med. 358, 1240-1249
   Abstract »    Full Text »    PDF »
Gene Discovery in Venous Thrombosis: Progress and Promise.
E. G. Bovill (2008)
JAMA 299, 1362-1363
   Full Text »    PDF »
Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked SNPs in the ANRIL locus on chromosome 9p.
H. M. Broadbent, J. F. Peden, S. Lorkowski, A. Goel, H. Ongen, F. Green, R. Clarke, R. Collins, M. G. Franzosi, G. Tognoni, et al. (2008)
Hum. Mol. Genet. 17, 806-814
   Abstract »    Full Text »    PDF »
A genome-wide association study of sporadic ALS in a homogenous Irish population.
S. Cronin, S. Berger, J. Ding, J. C Schymick, N. Washecka, D. G. Hernandez, M. J. Greenway, D. G. Bradley, B. J. Traynor, and O. Hardiman (2008)
Hum. Mol. Genet. 17, 768-774
   Abstract »    Full Text »    PDF »
Can Fishing for New Genes Catch Patients at Risk of Coronary Artery Disease?.
J. Emmerich and P. M Ridker (2008)
Clin. Chem. 54, 453-455
   Full Text »    PDF »
Chromosome 9p21.3 Coronary Heart Disease Locus Genotype and Prospective Risk of CHD in Healthy Middle-Aged Men.
P. J. Talmud, J. A. Cooper, J. Palmen, R. Lovering, F. Drenos, A. D. Hingorani, and S. E. Humphries (2008)
Clin. Chem. 54, 467-474
   Abstract »    Full Text »    PDF »
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.
G.-Q. Shen, L. Li, S. Rao, K. G. Abdullah, J. M. Ban, B.-S. Lee, J. E. Park, and Q. K. Wang (2008)
Arterioscler. Thromb. Vasc. Biol. 28, 360-365
   Abstract »    Full Text »    PDF »
Assessment of cumulative evidence on genetic associations: interim guidelines.
J. P. Ioannidis, P. Boffetta, J. Little, T. R O'Brien, A. G Uitterlinden, P. Vineis, D. J Balding, A. Chokkalingam, S. M Dolan, W D. Flanders, et al. (2008)
Int. J. Epidemiol. 37, 120-132
   Abstract »    Full Text »    PDF »
Commentary: Genetic association studies see light at the end of the tunnel.
T. M Frayling (2008)
Int. J. Epidemiol. 37, 133-135
   Full Text »    PDF »
Rationale, Design, and Methodology of the Women's Genome Health Study: A Genome-Wide Association Study of More Than 25 000 Initially Healthy American Women.
P. M Ridker, D. I. Chasman, R. Y.L. Zee, A. Parker, L. Rose, N. R. Cook, J. E Buring, and for the Women's Genome Health Study Working Group (2008)
Clin. Chem. 54, 249-255
   Abstract »    Full Text »    PDF »
Update on the Genetics of Stroke and Cerebrovascular Disease 2007.
R. A. Hegele and M. Dichgans (2008)
Stroke 39, 252-254
   Full Text »    PDF »
Surprises of the genome and "personalized" medicine..
A. J. Marian (2008)
J. Am. Coll. Cardiol. 51, 456-458
   Full Text »    PDF »
Required sample size and nonreplicability thresholds for heterogeneous genetic associations.
R. Moonesinghe, M. J. Khoury, T. Liu, and J. P. A. Ioannidis (2008)
PNAS 105, 617-622
   Abstract »    Full Text »    PDF »
Genome-Wide Association: Which Do You Want First: the Good News, the Bad News, or the Good News?.
K. D. Taylor, J. M. Norris, and J. I. Rotter (2007)
Diabetes 56, 2844-2848
   Full Text »    PDF »
Future Use of Genomics in Coronary Artery Disease.
S. B. Damani and E. J. Topol (2007)
J. Am. Coll. Cardiol. 50, 1933-1940
   Abstract »    Full Text »    PDF »
Validity of Reported Genetic Risk Factors for Acute Coronary Syndrome.
W. G. Feero, T. A. Manolio, A. E. Guttmacher, and F. S. Collins (2007)
JAMA 298, 1757
   Full Text »    PDF »
Validity of Reported Genetic Risk Factors for Acute Coronary Syndrome Reply.
T. M. Morgan, H. M. Krumholz, R. P. Lifton, and J. A. Spertus (2007)
JAMA 298, 1759
   Full Text »    PDF »
Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits.
A. Swaroop, K. E. Branham, W. Chen, and G. Abecasis (2007)
Hum. Mol. Genet. 16, R174-R182
   Abstract »    Full Text »    PDF »
Interpreting P Values in Pharmacogenetic Studies: A Call for Process and Perspective.
M. L. Maitland, M. J. Ratain, and N. J. Cox (2007)
J. Clin. Oncol. 25, 4513-4515
   Full Text »    PDF »
Genetics of Cardiovascular Diseases: From Single Mutations to the Whole Genome.
F. Cambien and L. Tiret (2007)
Circulation 116, 1714-1724
   Full Text »    PDF »
Genetic Susceptibility to Peripheral Arterial Disease: A Dark Corner in Vascular Biology.
J. W. Knowles, T. L. Assimes, J. Li, T. Quertermous, and J. P. Cooke (2007)
Arterioscler. Thromb. Vasc. Biol. 27, 2068-2078
   Abstract »    Full Text »    PDF »
Two Common Gene Variants on Chromosome 9 and Risk of Atherothrombosis.
R. Y.L. Zee and P. M Ridker (2007)
Stroke 38, e111
   Full Text »    PDF »
Tyrosine Hydroxylase: Another Piece of the Genetics of Hypertension Puzzle.
S. C. Hunt (2007)
Circulation 116, 970-972
   Full Text »    PDF »
Scanning the Genome for Coronary Risk.
A. Rosenzweig (2007)
N. Engl. J. Med. 357, 497-499
   Full Text »    PDF »
Genomewide Association Analysis of Coronary Artery Disease.
N. J. Samani, J. Erdmann, A. S. Hall, C. Hengstenberg, M. Mangino, B. Mayer, R. J. Dixon, T. Meitinger, P. Braund, H.-E. Wichmann, et al. (2007)
N. Engl. J. Med. 357, 443-453
   Abstract »    Full Text »    PDF »
The Genomics Gold Rush.
E. J. Topol, S. S. Murray, and K. A. Frazer (2007)
JAMA 298, 218-221
   Full Text »    PDF »
Allele on Chromosome 9 Affects Heart Disease Risk.
(2007)
Journal Watch (General) 2007, 6
   Full Text »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products