Candidate gene studies and GWAS: strengths and weaknesses

• Published in: Canadian journal of cardiology 2012, Vol.28 (3), p.296-304
• Main Authors: Delles, Christian, MD, FRCP, Padmanabhan, Sandosh, PhD, FRCP
• Format: Article
• Language: English
• Subjects: Cardiovascular
• ISSN: 0828-282X
• DOI: 10.1016/j.cjca.2012.02.004

Abstract Recent advances in genotyping technology and in particular a number of large-scale genome-wide association studies have helped to unravel the genetic basis of hypertension. Although our knowledge is still far from being complete it is important to ask how genetic findings could be translated to clinical practice. In a first step we summarize the strategies to dissect the genetics of hypertension from candidate gene studies to genome-wide association studies and recent sequencing experiments. The greatest hope in this context is the development of new drugs that are based on newly discovered pathophysiological principles. We describe examples where significant therapeutic effects are achieved with agents targeting pathways that contribute only small amounts to the genetic variability of a phenotype. There are good reasons to believe that new drugs will be developed based on genetic data in hypertension. We also highlight the potential for pharmacogenetics and risk stratification. The former is not currently supported by a larger body of evidence, but well designed studies are under way. The latter needs to follow the same principles for evaluation of other novel biomarkers of cardiovascular risk and is unlikely to influence clinical practice in the next few years.