CHOP Researcher Co-Leads Largest-Ever Gene Study of Blood Pressure in African Americans

09/12/2013

The largest-ever genetic analysis of blood pressure in African Americans has identified five gene variants linked to the trait. Three of the gene variants have not previously been implicated in blood pressure, and represent novel findings.

The study appeared online Aug. 22 in the American Journal of Human Genetics and in the September print issue.

“High blood pressure occurs in roughly 40 percent of African Americans, which is a much higher rate than in other U.S. ethnic groups, and adds a significant risk to the development of cardiovascular disease,” said geneticist Brendan J. Keating, D. Phil., of The Center for Applied Genomics at The Children’s Hospital of Philadelphia, and a faculty member in the Perelman School of Medicine at the University of Pennsylvania, one of the co-senior authors of the paper. “The discovery component of this study included data from nearly 30,000 African American individuals.” In the replication phase, the researchers validated the findings in over 100,000 individuals of different ancestries.

The research findings do not have immediate implications for treatment, but the hope is that discovering genes associated with disease risks will bring scientists closer to biological pathways and may suggest useful drug targets for new treatments.

The other two senior co-authors of the study are Xiaofeng Zhu, PhD, of Case Western Reserve University, Cleveland, and Nora Franceschini, MD, MPH, of the University of North Carolina, Chapel Hill. There were dozens of co-authors in this meta-analysis, which combined data from 19 cohorts of adult subjects who contributed their DNA to previous genome-wide association study (GWAS) analyses.

Three of the variants discovered in the African American samples, in the genes EVX1-HOXA, RSPO3 and PLEKHG1, had not previously been reported for blood pressure. Two other gene variants in those subjects had previously been discovered in patients of European ancestry.

“These findings actually explain only a very small portion of the genetic variation that we know underpins blood pressure in individuals of African ancestry, so further independent studies need to be added to these efforts to discover even more variants,” said Keating. “Gaining more biological knowledge of the factors underlying blood pressure levels will help us to obtain new insight into the development of hypertension and to identify potential new drug candidates for therapy.”

Contact: John Ascenzi, Children's Hospital of Philadelphia, 267-426-6055 or ascenzi@email.chop.edu.