The Cardiovascular Research Center at Massachusetts General Hospital


Sekar Kathiresan, MD

Sekar Kathiresan, MD

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Science

The goals of our laboratory are to:

1. Map genetic loci and the causal genes associated with blood lipid traits and risk of myocardial infarction (MI).

2. Develop a molecular understanding how causal variants and genes lead to phenotype .

3. Translate genetic discoveries to improve preventive cardiac care . The following are current research projects focused on the above goals: 1. Myocardial Infarction Genetics Consortium (MIGen). With collaborators, we have identified 9 genetic loci related to early-onset myocardial infarction (Nature Genetics 2009a). We seek to identify the full spectrum of allelic variation at each locus related to MI and at several of the novel loci, define the mechanisms by which the genes lead to atherosclerotic cardiovascular disease.

The following are current research projects focused on the above goals:

1. Myocardial Infarction Genetics Consortium (MIGen). With collaborators, we have identified 9 genetic loci related to early-onset myocardial infarction (Nature Genetics 2009a). We seek to identify the full spectrum of allelic variation at each locus related to MI and at several of the novel loci, define the mechanisms by which the genes lead to atherosclerotic cardiovascular disease.



Figure 1. MIGen in an international consortium composed of collaborators from 16 sites across the United States and Europe.

2. Genetics of blood lipids. Using genome-wide association methodology, we have identified 30 genetic loci related to blood LDL cholesterol, HDL cholesterol, or triglycerides (Nature Genetics 2008, Nature Genetics 2009b). Using mouse models, we are now focused on developing a molecular understanding of how the newly discovered genes influence plasma lipids. 3. Clinical application of genetic discoveries. We reported proof of concept that a panel of genetic polymorphisms may aid in predicting risk for cardiovascular disease (N Engl J Med 2008). We are now extending this work to include a more complete panel of risk variants and testing the external generalizability of our initial findings.

Publications
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Massachusetts General Hospital the cardiovascular research center