February 10, 2005 |
A first-of-its-kind application of a novel statistical method of analysis to African Americans has identified regions on chromosomes 6 and 21 that likely harbor genes contributing to high blood pressure in that group. The novel statistical method, called admixture mapping, narrowed the search for genes related to hypertension, bringing researchers and doctors closer to finding more effective treatments. Researchers at Stanford University School of Medicine, Loyola University Medical Center and Washington University School of Medicine in St. Louis, among others, collaboratively conducted the study, which will be published in the February issue of Nature Genetics and is available online.
In the U.S., 65 million people have high blood pressure, but it is found more often in African Americans than other groups. African Americans 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,” says Dabeeru C. Rao, Ph.D., director of the Division of Biostatistics and one of the report’s authors. “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 that compared 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 can 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 says.
“The admixture mapping method has distinct advantages over other more commonly used methods for population analysis,” says C. Charles Gu, Ph.D., assistant professor of biostatistics and a co-author of the report. “We looked for genomic regions with an ‘excess of ancestry’ from one of the two populations. In this case we looked for excess ancestry from the African population, because it has a higher frequency of genes contributing to high blood pressure.” Excess of ancestry is a term indicating the genomic region in African Americans is derived more often from one ancestral population than the other.
The researchers looked at the distribution of 269 genetic markers across the genome in each of the three groups. Compared to 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 of markers probably contain genes responsible for an increased risk of hypertension.
Researchers can now use this information to help locate genes affecting 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 says. “In addition, research institutions and pharmaceutical companies can develop new drugs that compensate for the effect of that gene.”
Data used in the study 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 at Washington University serves as the Program Data Center for the Family Blood Pressure Program, which involves twenty institutions, including those participating in this project. The division pools and integrates data from across different study centers and makes the data available to all the participants. It will build a web-based system to open the data to the public. This particular project was led by Neil Risch at Stanford and the analysis was led by Xiofeng Zhu at Loyola.