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Published Online May 3, 2007
Science DOI: 10.1126/science.1142842

Reports

Submitted on March 21, 2007
Accepted on April 26, 2007

A Common Variant on Chromosome 9p21 Affects the Risk of Myocardial Infarction

Anna Helgadottir 1, Gudmar Thorleifsson 1, Andrei Manolescu 1, Solveig Gretarsdottir 1, Thorarinn Blondal 1, Aslaug Jonasdottir 1, Adalbjorg Jonasdottir 1, Asgeir Sigurdsson 1, Adam Baker 1, Arnar Palsson , Gisli Masson 1, Daniel Gudbjartsson 1, Kristinn P. Magnusson 1, Karl Andersen 2, Allan I. Levey 3, Valgerdur M. Backman 1, Sigurborg Matthiasdottir 1, Thorbjorg Jonsdottir 1, Stefan Palsson 1, Helga Einarsdottir 1, Steinunn Gunnarsdottir 1, Arnaldur Gylfason 1, Viola Vaccarino 3, W. Craig Hooper 3, Muredach P. Reilly 4, Christopher B. Granger 5, Harland Austin 3, Daniel J. Rader 4, Svati H. Shah 5, Arshed A. Quyyumi 3, Jeffrey R. Gulcher 1, Gudmundur Thorgeirsson 3, Unnur Thorsteinsdottir 1, Augustine Kong 1*, Kari Stefansson 1*

1 deCODE genetics Inc, Reykjavik, Iceland.
2 National University Hospital, Reykjavik, Iceland.
3 Emory University School of Medicine, Atlanta, GA 30322, USA.
4 University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
5 Duke University School of Medicine, Durham, NC 27710, USA.

* To whom correspondence should be addressed.
Augustine Kong , E-mail: augustine.kong{at}decode.is
Kari Stefansson , E-mail: kstefans{at}decode.is

The global endemic of cardiovascular diseases calls for improved risk assessment and treatment. Here we describe an association between myocardial infarction (MI) and a common sequence variant on chromosome 9p21. This study included a total of 4587 cases and 12,769 controls. The identified variant, adjacent to the tumor suppressor genes CDKN2A and CDKN2B, was associated to the disease with high significance (P = 1.2 x 10-20). Approximately 21% of individuals in the population are homozygous for this variant and they have an estimated 1.64-fold greater risk of suffering myocardial infarction than non-carriers. The corresponding risk is 2.02-fold for early onset cases. The population attributable risk (PAR) is 21% for MI in general and 31% for early onset cases.


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