In one of the largest studies of its kind, an international research team has discovered more than 200 new genetic variations associated with high blood pressure.
The research was led by 20 Vanderbilt University scientists.
The study also identified specific tissues where blood pressure genes exert their effects as well as a long list of drugs that act upon those genes.
While large swaths of the map remain to be filled in, the researchers said they are closer than ever to being able to improve the treatment of high blood pressure based on the patient’s genetic make-up.
In the study, the team analyzed the relationship between genetic variants and blood pressure traits utilizing the electronic health records of more than 300,000 participants in the Million Veteran Program (MVP) and more than 140,000 participants in the UK (United Kingdom) BioBank study.
The researchers then replicated their findings by analyzing 17,000 samples from the Vanderbilt University biobank, BioVU, and 300,000 from large genetic consortia of blood pressure studies.
MVP is a national effort by the U.S. Department of Veterans Affairs (VA) to collect blood samples and health information from one million veteran volunteers.
Thirty percent of the participants in the MVP portion of the study were African-Americans, Hispanics, Asians and Native Americans—making this one of the most racially diverse genetic inquiries of its kind.
The kidney disease/hypertension beta grant was one of the four first grants awarded to use the MVP “mega” biobank.
Since MVP was launched in 2011, the biobank has collected samples from more than 700,000 veteran volunteers recruited through 63 VA medical centers across the country.
Locally, the researchers have signed up 20,000 veterans, making her “one of the most successful (MVP) recruiters in the United States.
Another unique aspect of the Vanderbilt-led study is that it analyzed not only the impact that genetic variation has on blood pressure but also how genetically-predicted changes in the expression or activity level of other genes can influence, in subtle ways, the physiology of tissues throughout the body.
Using GTEx (Genotype-Tissue Expression), a reference data set of genetic variations and gene activity in multiple healthy tissues developed by the National Institutes of Health (NIH), researchers at the University of Chicago developed a method for predicting how changes in gene expression may contribute to disease.
The researchers, Nancy Cox, Ph.D., Eric Gamazon, Ph.D., and their colleagues have since moved to Vanderbilt.
Their technique, called PrediXcan, has become a powerful tool for discovering the genetic underpinnings of diseases as diverse as type 1 diabetes, rheumatoid arthritis and bipolar disorder.
In the current study, the researchers used S-PrediXcan, a modified version of the PrediXcan method, to detect associations between genetically-predicted gene expression of 840 unique genes in 45 tissues and observed blood pressures (those recorded in veterans’ electronic health records).
Not only did the researchers identify genes that are potential targets for the development of new drugs, but using genes identified from S-PrediXcan together with bioinformatics-related approaches, they also identify drugs currently on the market for other uses that potentially could be “re-purposed” as anti-hypertensive medications.
Todd Edwards, Ph.D., associate professor of Medicine in the Vanderbilt University School of Medicine, is one of two senior corresponding authors with Adriana Hung, MD, MPH.
The study is published in the journal Nature Genetics.
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Source: Nature Genetics.
