Blood Pressure Genes

Study finds 500 new blood pressure genes

An analysis of the genomes of more than 1 million people of European ancestry, conducted by several of the world’s leading genomic centers, including Vanderbilt University Medical Center, has identified more than 2,000 independent genetic signals for blood pressure.

An analysis of the genomes of more than 1 million people of European ancestry, conducted by several of the world’s leading genomic centers, including Vanderbilt University Medical Center, has identified more than 2,000 independent genetic signals for blood pressure.

The findings, published April 30 in the journal Nature Genetics, include improved polygenic scores for predicting blood pressure and the discovery of 500 previously unreported genes that affect blood pressure.

This knowledge can be used to identify potential new drug targets, and to advance precision medicine in the early detection and prevention of hypertension (high blood pressure).

Data obtained from the study were used to generate polygenic risk scores, which combine the potential health effects of hundreds to thousands of genetic variations.

These scores also reflected genetic risk for hypertension in people of both European and African American ancestry. The latter group has historically been underrepresented in genetic studies.

“Our results demonstrate that the biology of blood pressure is highly complex and polygenic, influenced by thousands of single nucleotide polymorphisms (genetic variants) with extremely subtle effect sizes,” the researchers concluded.

“These associations explain large differences in average blood pressure between individuals and have a very strong influence on risk of hypertension,” they continued. “This study is … another key step toward understanding one of the most complex and highly regulated biological systems in humans that has significant implications for health, disease treatment and prevention.”

Todd Edwards, PhD

“In principle, if your doctor knew your genotype and used our model, (he or she) could predict with some level of accuracy whether you would go on to develop hypertension,” said Todd Edwards, PhD, associate professor of Medicine at VUMC and associate director of the Vanderbilt Genetics Institute.

“Once genotype data become widely available … it could be a good prognostic indicator,” said Edwards, a corresponding author of the paper with Helen Warren, PhD, from Queen Mary University of London, England, and Ahmad Vaez, MD, PhD, at the University of Groningen in the Netherlands.

The study combined previously published and de-identified genetic data from about 450,000 individuals provided by the UK Biobank, the International Consortium for Blood Pressure (about 300,000 individuals), and the U.S. Department of Veterans Affairs’ Million Veteran Program (about 220,000 individuals), with new data from VUMC’s biorepository, BioVUBioVU (about 50,000 individuals).

With a sample size of more than 1 million people of European descent, this was the largest single-stage, genome-wide association study (GWAS) for blood pressure conducted to date.

Using PrediXcan, a technique for predicting how changes in gene expression may contribute to hypertension, the researchers identified associations between hundreds of genes that have an impact on blood pressure.

The technique was developed at the University of Chicago by researchers who later moved to VUMC including Nancy Cox, PhD, who directs the Vanderbilt Genetics Institute, Eric Gamazon, PhD, and their colleagues. 

Jacob Keaton, PhD

One of the genes found to be associated with blood pressure is involved in iron metabolism and iron overload, suggesting that “altered iron metabolism may play a role in blood pressure regulation and hypertension-related cardiovascular disease,” the researchers reported.

The paper’s first author, Jacob Keaton, PhD, is a former postdoctoral research fellow at VUMC in the Edwards lab who is now at the National Human Genome Research Institute, part of the National Institutes of Health.

Keaton was responsible for many of the primary analyses in the paper, “and he did a substantial amount of the writing, implementing other people’s ideas,” Edwards said.

More than 140 investigators from more than 100 universities, institutes, and government agencies throughout the world contributed to the study. Other VUMC co-authors were Jacklyn Hellwege, PhD, Ayush Giri, PhD, and Yingchang Lu, MD, PhD.

blood pressure, hypertension, genes, genetic predisposition, renin-angiotensin system, sodium regulation, vascular function, heart disease, stroke, kidney problems, genome-wide association studies, GWAS, loci, personalized treatments, preventative strategies, lifestyle modifications, medication, genetic susceptibility, cardiovascular health, risk factors, genetic research,

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