Abstract
Several high-profile failures of lipid-related therapeutics in clinical trials have led to intense interest in improved discovery and preclinical prioritization of potential targets. The careful study of patients with rare monogenic disorders has played a key role in establishing the causal role of cholesterol in atherosclerosis and highlighting viable drug targets. Systematic efforts to extend the association of common variants linked with lipid levels to coronary disease enable assessment of the vascular consequences of lifelong differences in lipids due to variation in specific molecules. This application of genetic epidemiology, termed Mendelian randomization, may prove useful in informing ongoing drug development efforts.
(c) 2009 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Biomarkers / blood
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Cardiovascular Diseases / genetics
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Cardiovascular Diseases / metabolism
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Cardiovascular Diseases / prevention & control*
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Cholesterol, HDL / blood
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Cholesterol, LDL / blood
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Drug Discovery / methods*
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Dyslipidemias / drug therapy*
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Dyslipidemias / genetics
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Dyslipidemias / metabolism
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Genetic Predisposition to Disease
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Genomics*
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Humans
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Hypolipidemic Agents / chemistry
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Hypolipidemic Agents / pharmacology
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Hypolipidemic Agents / therapeutic use*
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Lipid Metabolism / drug effects*
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Lipid Metabolism / genetics
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Lipoprotein(a) / blood
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Mendelian Randomization Analysis
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Phenotype
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Polymorphism, Genetic
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Reproducibility of Results
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Treatment Outcome
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Triglycerides / blood
Substances
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Biomarkers
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Cholesterol, HDL
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Cholesterol, LDL
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Hypolipidemic Agents
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Lipoprotein(a)
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Triglycerides