Advances in blood pressure genomics

Abstract

The elucidation of genes implicated in Mendelian forms of hypertension demonstrates rare variants with substantial effects are responsible, and often these genes lie within pathways managing sodium homeostasis. More recently with advances in affordable high-throughput genotyping strategies, multiple common genetic variants with modest effects on blood pressure (<1 mmHg systolic) have been discovered in the population. In aggregate, these common variants explain <3% of the variance of blood pressure. Although these findings may offer new mechanistic insights into the biology of blood pressure, a key question is can these findings translate into patient benefit? It is timely to reflect on recent advances in genomics, and the use of new resources, such as the 1000 Genomes Project and the Encyclopedia of DNA Elements, to annotate likely causal variants, and their relevance to cardiovascular disease. In this review, we discuss the advances in relation to our knowledge of the genetic architecture of blood pressure, and whether gene discoveries might influence cardiovascular risk assessment, help to stratify patient response to medicine, or identify new biological pathways for novel therapeutic targets.

Keywords: 1000 genome; blood pressure; exome; genome-wide association studies; next generation sequencing; pharmacogenomics.