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New Genes Implicated in High Blood Pressure Regulation

By LabMedica International staff writers
Posted on 27 Sep 2016
High blood pressure, or hypertension, affects one in three adults in the USA, according to the government authorities. The condition increases the risk for heart disease and stroke, but most people with high blood pressure are not aware they have it.

Several large international groups of scientists report data that more than doubles the number of sites in the human genome tied to blood pressure regulation. One of the studies turned up unexpected hints that biochemical signals controlling blood pressure may spring from within cells that line blood vessels themselves.

In one study conducted by scientists at Johns Hopkins University School of Medicine (Baltimore, MD, USA) and the colleagues examined participants’ genomes on computer-chiplike devices known as microarrays, which had been customized to simultaneously analyze nearly 200,000 sites in the genome where variations from person to person were suspected to have some effect on blood pressure. They then compared variants at the sites with information on each individual’s blood pressure information to confirm likely associations. To dissect the genetic architecture of blood pressure and assess effects on target organ damage, they analyzed 128,272 single nuclear polymorphisms (SNPs) from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation.

The teams identified 66 blood pressure–associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney.

One surprising finding from the study was that many of the new sites identified were near genes that are active in cells that line the inside of blood vessels, suggesting those cells are somehow involved directly in blood pressure control. Aravinda Chakravarti, PhD, a professor of medicine and a lead investigator, said, “It is thought that about half the explanation for our blood pressure comes from environmental and lifestyle factors, like diet, exercise and smoking, and the other half is controlled by our genes, but as with many other complex, multigene traits, pinning down what those genes are is challenging.” The study was published on September 12, 2016, in the journal Nature Genetics.

Related Links:
Johns Hopkins University School of Medicine


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