Leveraging human genetics to guide drug target discovery.
Identifying appropriate molecular targets is a critical step in drug development. Despite many advantages, the traditional tools of observational epidemiology and cellular or animal models of disease can be misleading in identifying causal pathways likely to lead to successful therapeutics. Here, we review some favorable aspects of human genetics studies that have the potential to accelerate drug target discovery. These include using genetic studies to identify pathways relevant to human disease, leveraging human genetics to discern causal relationships between biomarkers and disease, and studying genetic variation in humans to predict the potential efficacy and safety of inhibitory compounds aimed at molecular targets. We present some examples taken from studies of plasma lipids and coronary artery disease to highlight how human genetics can accelerate therapeutics development.
Cardiovascular Division, Department of Medicine, Washington University School of Medicine, Saint Louis, MO; Department of Genetics, Washington University School of Medicine, Saint Louis, MO; McDonnell Genome Institute, Washington University School of Medicine, Saint Louis, MO. Electronic address: nstitziel@wustl.edu.
Nathan O
NO
Stitziel
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA. Electronic address: skathiresan@partners.org.
Sekar
S
Kathiresan
D000818:Animals; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D055808:Drug Discovery / Q000379:methods*; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D058990:Molecular Targeted Therapy; D010597:Pharmacogenetics; D010641:Phenotype; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects
D002317:Cardiovascular Agents
Cardiovascular disease; Human genetics
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