Genomics is a discipline in genetics that applies recombinant DNA, DNA sequencing methods, and bioinformatics to sequence, assemble, and analyze the function and structure of genomes, the complete set of DNA within a single cell of an organism. Research into the genetics of hypertension has now expanded to genomics. Two approaches have dominated this field. One relies on large populations in which the phenotype, hypertension versus no hypertension, or hypertension-relevant phenotypes are compared. Genome-wide association (GWAS) analyses of (>1 million) common variants identify relevant loci and possible genes exerting small effects. Detailed studies on APOL1 and SH2B3 are opening entire new fields of research. Family-based Mendelian studies have identified rare variants that exert very large effects on blood pressure. Mechanistically, these studies have been a bonanza of new information. The approaches are complementary.
Genome-wide association studiesEssential (primary) hypertension results from many environmental and genetic factors.Candidate-gene, genome-wide linkage, and genome-wide association studies (GWAS) relying on single-nucleotide polymorphisms (SNPs) have all given insights into genes relevant for essential hypertension. Candidate gene studies have implicated aberrations in aldosterone signaling, catecholamine pathways, ion channel regulation, and inflammatory pathways. For GWAS, massive sample sizes have been used (>80,000 individuals) to find gene loci that exert only modest effects. Memorizing these genes and their variants seems counterproductive since thus far they collectively explain only about 2.5% of blood pressure variation. Nevertheless, ranking all the currently known findings could theoretically produce a genetic risk score indicating a 25% increase in the odds of developing essential hypertension.High-throughput massive parallel sequencing and the plummeting costs (currently about