A new report from scientists at Massachusetts General Hospital (MGH) and their colleagues in centers around the world finds that common variants in 28 regions of DNA are associated with blood pressure in human patients. Of the identified regions, most were completely unsuspected, although some harbor genes suspected of influencing blood pressure based on animal studies. In the study receiving advance online publication in Nature, members of the International Consortium for Blood Pressure Genome-Wide Association Studies (ICBP-GWAS) analyzed genetic data from over 275,000 individuals from around the world. They also identified for the first time the involvement of an important physiologic pathway in blood pressure control, potentially leading to a totally new class of hypertension drugs.
“Identifying these novel pathways expands our current understanding of the determinants of blood pressure and highlights potential targets for new drugs to treat and prevent cardiovascular complications,” says Christopher Newton-Cheh, MD, MPH, of the MGH Center for Human Genetic Research and the Cardiovascular Research Center, co-chair of the ICBP-GWAS Steering Committee and a senior and corresponding author on the Nature paper.
It is well known that hypertension can run in families and that some rare genetic syndromes raise blood pressure, but identifying genes associated with the common form of hypertension has been challenging. To get a study sample large enough to detect variants with modest effects, ICBP-GWAS researchers conducted a meta-analysis of 30 genome-wide association studies that included measurements of participants’ blood pressures. Analysis of 2.5 million DNA sequence variants in more than 69,000 individuals of European ancestry identified several chromosomal regions where genes influencing blood pressure appeared to be located. To confirm the results of the first-stage analysis, the researchers genotyped the strongest variants in more than 133,000 additional individuals of European descent. Combining the results identified 28 gene regions associated with both systolic and diastolic blood pressure, of which 16 were novel. A second paper from the consortium also receiving online publication today in Nature Genetics, identified six additional novel variants…
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