An update on genome-wide association studies of hypertension

Abstract

Hypertension is a major global health problem associated with cardiovascular and cerebrovascular diseases. It is well established that blood pressure and hypertension are common complex phenotypes affected by multiple genetic and environmental factors. Contemporary genomic tools make it possible to genotype millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, which has transformed hypertension genetics research. International collaborations/consortia have enabled the use of unprecedentedly large sample sizes for gene discovery and replication. Genome-wide association studies have reported more than 60 loci associated with blood pressure or hypertension, most of which were not expected to have any association with these phenotypes. In contrast to linkage and candidate gene studies, the reproducibility of genome-wide association studies is much higher and some results have been verified across different ethnicities. These novel findings have provided potential targets for pharmacotherapy and clues for personalized prevention and treatment of hypertension. Although only a small proportion of blood pressure variation is attributed to the genetic variants identified so far, more variants are likely to be discovered by employing larger sample sizes, studying gene–environment interactions, or by exploring low-frequency or rare variants. Advances in epigenetics, which examines trait variation not caused by differences in DNA sequences, will probably reveal a new and important class of genetic components for hypertension.