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Study expands number of known blood pressure genetic associations

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Three large, collaborating international consortia of researchers, including a team co-led by investigators from Brigham and Women's Hospital (BWH), have uncovered new genes and sites in the genome tied to elevated blood pressure, implicating certain biological pathways and pointing toward new therapeutic strategies for treating hypertension. In one of three papers published simultaneously in Nature Genetics on Sept. 12, Daniel Chasman, PhD, associate geneticist at BWH, and colleagues report on 31 novel loci (specific locations in the genome) that can now be tied to blood pressure levels. Before the new publications, researchers had identified genetic variants at approximately 60 loci associated with blood pressure. Together, the three papers together double the number of known loci for blood pressure.

"Our work greatly extends the number of known blood-pressure-associated loci and demonstrates their potential relevance to cardiovascular disease," said Chasman, senior author of one of the Nature Genetics studies and an associate professor at Harvard Medical School. "These new blood pressure studies have suddenly expanded what's known about biological basis of hypertension, and may help guide us and others to new ways to detect, manage and treat this all-too common risk factor for serious health problems, such as heart attack and stroke."

Hypertension, or high blood pressure, can put individuals at risk for a number of diseases, including heart disease and chronic kidney disease, and is a risk factor for overall mortality. More than 70 million Americans – about one in every three adults – have high blood pressure and only about half have their condition under control, according to the Centers for Disease Control and Prevention.

In the new work, members of the NHLBI-funded CHARGE Consortium collected genetic data at specific sites in the genome using the Human Exome BeadChip. These data were derived from more than 146,000 individuals of European, African, and Hispanic ancestry, including participants from the Women's Genome Health Study, a population-based cohort overseen by investigators in the Division of Preventive Medicine at BWH. Promising associations with blood pressure were verified in data from a parallel effort from a UK-based consortium for a total combined sample exceeding 325,000 individuals.

While many of the newly reported genetic variants can be linked to known biological mechanisms of blood pressure regulation, fourteen variants reside in loci that have been previously associated only with somewhat unexpected biological pathways, including those related to immunologic diseases, diabetes, kidney function and more, thus establishing new connections between blood pressure and other clinical conditions. For example, the new findings point to a gene that plays a role in insulin secretion, which is closely related to type 1 and type 2 diabetes, and other genes that have been associated with Crohn's disease and lupus.

"The overlap of these genetic variants with immunologic and metabolic diseases suggests that there may be common underlying causes for elevated blood pressure and other metabolic risk factors," said Chasman. "This may also serve as a starting point for finding therapies that can more broadly treat hypertension to reduce cardiovascular risk."

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The Women's Genome Health Study is funded by the National Heart, Lung and Blood Institute and the National Cancer Institute with additional funding for genotyping provided by Amgen. Funding for infrastructure of the CHARGE consortium is provided by the NHLBI.

Paper cited:

Liu C. et al. "Novel Common and Rare Blood Pressure Loci Enriched for Metabolic Traits." Nature Genetics DOI: 10.1038/ng.3660

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 4.2 million annual patient visits and nearly 46,000 inpatient stays, is the largest birthing center in Massachusetts and employs nearly 16,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 3,000 researchers, including physician-investigators and renowned biomedical scientists and faculty supported by nearly $666 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative as well as the TIMI Study Group, one of the premier cardiovascular clinical trials groups. For more information, resources and to follow us on social media, please visit BWH's online newsroom.

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Haley Bridger
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