Genome-Wide Association Studies (Gwas) of Blood Pressure in Different Populations

Abstract

Hypertension represents a global public health burden. In addition to the rarer Mendelian forms of hypertension, classic genetic studies have documented a significant heritable component to the most common form, essential hypertension. Several strategies have been developed to identify a genetic variation that is associated with hypertension. Genome-wide association studies (GWAS) were developed to identify particular genetic markers (single-nucleotide polymorphism, SNP) that co-occur with blood pressure or hypertension. In GWAS, one human DNA sample can be queried for millions of genetic variants simultaneously, and the whole genome can be compared between different subjects. In addition, GWAS offer the potential to identify novel mechanisms in the pathophysiology of hypertension (HTN). To date, close to 30 GWAS and meta-analyses of GWAS have been conducted identifying over 100 SNPs in and around 86 genes. Unfortunately, GWAS, once felt to be revolutionizing the search for the genes underlying human complex diseases, have failed to deliver on the promise of identifying common genetic variants responsible for a large heritable portion of hypertension. Very few of the SNPs identified have been replicated in more than one study and more than one population group. However, improvement in our understanding of sample-size requirements, refinement in the type of gene chips with almost ~ 2.5 million SNPs, and development of high-throughput sequencing may breathe fresh life into this strategy.