Genome Study Results May Lead to Genetic Test for Hypertension

    Several large international teams of researchers report data in Nature Genetics that more than doubles the number of sites in the human genome tied to blood pressure regulation. One of the studies (“The Genetics of Blood Pressure Regulation and Its Target Organs from Association Studies in 342,415 Individuals”) by Johns Hopkins University scientists, in collaboration with many other groups, turned up unexpected hints that biochemical signals controlling blood pressure may spring from within cells that line the blood vessels themselves.

    “It’s 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,” says Aravinda Chakravarti, Ph.D., professor of medicine in the Johns Hopkins University School of Medicine’s McKusick-Nathans Institute of Genetic Medicine and leader of the Johns Hopkins component. “But as with many other complex, multigene traits, pinning down what those genes are is challenging.”

    Prior to the new studies now reported, notes Dr. Chakravarti, about 90 sites in the genome had been identified as likely linked to blood pressure regulation. But in sum, they could not explain all variations in blood pressure measurements. To find what the scientists were convinced had to be more sites, researchers from 265 institutions worldwide banded together to perform the genomewide association study.

    Participants’ genomes were examined on microarrays, which had been customized to analyze nearly 200,000 sites simultaneously 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 nail down likely associations.

    Georg Ehret, M.D., a research associate in Dr. Chakravarti’s lab, crunched the numbers from all the study sites and found variants at 66 sites in the genome—17 of them newly reported—that had statistically significant associations with blood pressure levels. At the same time, Drs. Ehret and Chakravarti were also involved in another of the studies reported in the new issue of Nature Genetics. That study identified 31 additional and distinct new blood pressure-related sites and confirmed a further 39 that had been previously reported. It used data from 327,288 people and focused on rare genetic variants.

    Still, says Dr. Ehret, “even taking all the known variants together, we explain only about 2% to 3% of the blood pressure variability between individuals.” He estimates there are “hundreds or thousands” of blood pressure-linked variants still to be found and says identifying them will require studies with even more participants. One benefit of gathering those missing genetic puzzle pieces would be to enable a genetic test to predict whether a person is likely to develop high blood pressure and, if so, would suggest early intervention.

    One surprising finding from 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. “As a physician, I would have suspected the kidney, and perhaps the adrenal gland, of sending signals to control blood pressure,” points out Dr. Egret. “But it seems that the blood vessels themselves may also be part of the cause of hypertension.”