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Originally published in Science Express on 3 May 2007
Science 8 June 2007:
Vol. 316. no. 5830, pp. 1491 - 1493
DOI: 10.1126/science.1142842
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Reports

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,1 Gisli Masson,1 Daniel F. 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,2 Unnur Thorsteinsdottir,1 Augustine Kong,1{dagger} Kari Stefansson1{dagger}

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 12,767 controls. The identified variant, adjacent to the tumor suppressor genes CDKN2A and CDKN2B, was associated with the disease with high significance. Approximately 21% of individuals in the population are homozygous for this variant, and their estimated risk of suffering myocardial infarction is 1.64 times as great as that of noncarriers. The corresponding risk is 2.02 times as great for early-onset cases. The population attributable risk is 21% for MI in general and 31% for early-onset cases.

1 deCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
2 Landspitali 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.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: augustine.kong{at}decode.is (A.K.); kstefans{at}decode.is (K.S.)

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