Hypertension in African-Americans connected with two genomic regions

A first-of-its-kind statistical method has identified regions on chromosomes 6 and 21 that likely harbor genes contributing to high blood pressure in African-Americans.

The novel method, called admixture mapping, narrowed the search for genes related to hypertension, bringing researchers and doctors closer to finding more effective treatments.

Dabeeru Rao
Dabeeru Rao

Researchers at Washington University, Stanford University and Loyola University Medical Center, among others, conducted the study, which is published in the February issue of Nature Genetics.

In the United States, 65 million people have high blood pressure. But it is found more frequently in African-Americans, who suffer from earlier and more severe hypertension and have a higher rate of death from stroke, heart disease and kidney failure as a result.

The causes of hypertension are complex. Diet, exercise and stress contribute, but so do genetic factors.

“It wouldn’t be surprising if hypertension involved dozens of genes,” said study co-author Dabeeru C. Rao, Ph.D., director of the WUSTL Division of Biostatistics. “Unfortunately, in the past there have been conflicting reports about genes linked to the condition.”

In a fresh approach to the problem, the researchers applied a genome-wide scan comparing how often genetic variations occur in people of African or European descent to how often they occur in African-Americans.

As a group, African-Americans trace their ancestry largely to populations from both Africa and Europe.

“The statistical technique we used is ideal for groups who have a trait with a higher occurrence — such as hypertension in African-Americans — and who stem from two sets of ancestral populations that have differing genetic variations,” Rao said.

“The admixture mapping method has distinct advantages over other more commonly used methods for population analysis,” said co-author C. Charles Gu, Ph.D., assistant professor of biostatistics. “We looked for genomic regions where there is an ‘excess of ancestry’ from the population with a higher frequency of genes contributing to high blood pressure.”

Excess of African ancestry of a genomic region in hypertensives indicates that it is derived more often than other regions in the genome from ancestral African populations.

The researchers looked at the distribution of 269 genetic markers across the genome in each of the three groups. Compared with African-Americans without high blood pressure, African-Americans with high blood pressure were more likely to have a distribution of markers in the identified genomic regions resembling that of the African ancestral group.

The “excess” African ancestry among people with high blood pressure enabled the researchers to find two locations, one on chromosome 6 and one on chromosome 21, that stood out with the strongest association to high blood pressure in African-Americans.

Other markers close by on the same chromosomes also had a strong association with high blood pressure, indicating that the chromosome regions near these two groups probably contain genes responsible for an increased risk of hypertension.

“When a specific gene variant associated with hypertension is identified, physicians will be able to test patients for their risk of hypertension to head it off early,” Rao said. “In addition, research institutions and pharmaceutical companies can develop new drugs that compensate for the effect of that gene.”

Study data came from the U.S. National Heart, Lung, and Blood Institute’s Family Blood Pressure Program and the International Collaborative Study on Hypertension in Blacks.

The Division of Biostatistics serves as the Program Data Center for the Family Blood Pressure Program, which involves 20 institutions.