Scientists present genetic blueprint for blood pressure

In a comprehensive study published in Nature Genetics, researchers identified more than 100 new genomic loci that influence blood pressure, using data from more than one million participants. The findings, which also relate to iron metabolism and adrenergic receptors, could lead to new treatments for hypertension. Credit: SciTechDaily.com

More than 100 new genomic regions linked to blood pressure were discovered, providing insights into iron metabolism and potential new drug targets to treat hypertension.

The NIH-led study finds genetic markers that explain up to 12% of the differences between two people’s blood pressure.

National Institutes of Health (NIH) researchers and collaborators have discovered more than 100 new regions of the human genome, also known as genomic loci, that appear to influence a person’s blood pressure. The study results also point to several specific genomic loci that may be relevant to iron metabolism and a type of cell receptor known as adrenergic receptors.

The study, recently published in the journal Genetics of nature, is one of the largest genomic studies of blood pressure to date, including data from more than 1 million participants and laying the groundwork for researchers to better understand how blood pressure is regulated. This knowledge could point to possible new pharmaceutical targets.

The NIH-led study finds genetic markers that explain up to 12% of the differences between two people’s blood pressure. Credit: Darryl Leja, National Human Genome Research Institute

“Our study helps explain a much larger proportion of the differences between two people’s blood pressure than was previously known,” said Jacob Keaton, Ph.D., staff scientist in the Section of Health Informatics of Precision of the National Human Genome Research Institute (NHGRI) Intramural Research Program and first author of the study. “Our study found additional genomic locations that together explain a much larger portion of genetic differences in people’s blood pressure. Knowing a person’s risk of developing hypertension could lead to tailored treatments, which have more likely to be effective.”

To understand the genetics of blood pressure, the researchers combined four large datasets from genome-wide association studies of blood pressure and hypertension. After analyzing the data, they found more than 2,000 genomic loci linked to blood pressure, including 113 new regions. Among the newly discovered genomic loci, several reside in genes that play a role in iron metabolism, confirming previous reports that high levels of accumulated iron may contribute to cardiovascular disease.

Potential for new treatments for blood pressure

The researchers also confirmed the association between ADRA1A gene variants and blood pressure. ADRA1A encodes a type of cell receptor, called an adrenergic receptor, that is currently a target for blood pressure medication, suggesting that other genomic variants discovered in the study may also have the potential to be targets for drugs to alter blood pressure.

“This study shows that these large genome-wide association studies have clinical relevance for finding new drug targets and are needed to discover more drug targets as we move forward,” said Dr. Keaton.

From these analyses, the researchers were able to calculate a polygenic risk score, which combines the effects of all genomic variants to predict blood pressure and hypertension risk. These risk scores consider which genomic variants confer hypertension risk and reveal clinically meaningful differences between people’s blood pressure.

Polygenic risk scores have the potential to serve as a useful tool in precision medicine, but more diverse genomic data are needed to make them broadly applicable to routine health care. Although the data collected was mostly from people of European ancestry (due to the limited availability of several data sets when the study began), the researchers found that the polygenic risk scores were also applicable to people of African ancestry, which was confirmed by analyzing data from NIH’s All of Us Research Program, a national effort to build one of the largest biomedical data resources and accelerate research to improve human health.

The prevalence and risks of hypertension

Nearly half of adults in the United States have high blood pressure, known as hypertension. High blood pressure often runs in families, meaning there is a genetic component to developing the condition, in addition to environmental contributions such as a high-salt diet, lack of exercise, smoking and Stress. When blood pressure is consistently too high, it can damage the heart and blood vessels throughout the body, increasing the risk of heart disease, kidney disease, stroke and other conditions.

To learn more about this research, see 2,000 genetic signals linked to blood pressure discovered in study of more than a million people.

Reference: “Genome-Wide Analysis in Over 1 Million Individuals of European Descent Improves Polygenic Risk Scores for Blood Pressure Traits” by Jacob M. Keaton, Zoha Kamali, Tian Xie, Ahmad Vaez , Ariel Williams, Slavina B. Goleva, Alireza Ani , Evangelos Evangelou, Jacklyn N. Hellwege, Loic Yengo, William J. Young, Matthew Traylor, Ayush Giri, Zhili Zheng, Jian Zeng, Daniel I. Chasman, Andrew P. Morris, Mark J. Caulfield, Shih-Jen Hwang, Jaspal S. Kooner, David Conen, John R. Attia, Alanna C. Morrison, Ruth JF Loos, Kati Kristiansson, Reinhold Schmidt, Andrew A. Hicks, Peter P. Pramstaller, Christopher P .Nelson, Nilesh J. Samani, Lorenz Risch, Ulf Gyllensten, Olle Melander, Harriette Riese, James F. Wilson, Harry Campbell, Stephen S. Rich, Bruce M. Psaty, Yingchang Lu, Jerome I. Rotter, Xiuqing Guo, Kenneth M. Rice, Peter Vollenweider, Johan Sundström, Claudia Langenberg, Martin D. Tobin, Vilmantas Giedraitis, Jian’an Luan, Jaakko Tuomilehto, Zoltan Kutalik, Samuli Ripatti, Veikko Salomaa, Giorgia Girotto, Stella Trompet, J. Wouter Jukema, Pim van der Harst, Paul M. Ridker, Franco Giulianini, Veronique Vitart, Anuj Goel, Hugh Watkins, Sarah E. Harris, Ian J. Deary, Peter J. van der Most, Albertine J. Oldehinkel, Bernard D. Keavney, Caroline Hayward , Archie Campbell, Michael Boehnke, Laura J. Scott , Thibaud Boutin, Chrysovalanto Mamasoula, Marjo-Riitta Järvelin, Annette Peters, Christian Gieger, Edward G. Lakatta, Francesco Cucca, Jennie Hui, Paul Knekt, Stefan Enroth, Martin H. De Borst, Ozren Polašek, Maria Pina Concas, Eulalia Catamo , Massimiliano Cocca, Ruifang Li-Gao, Edith Hofer, Helena Schmidt, Beatrice Spedicati, Melanie Waldenberger, David P. Strachan, Maris Laan, Alexander Teumer, Marcus Dörr, Vilmundur Gudnason, James P. Cook, Daniela Ruggiero, Ivana Kolcic, Eric Boerwinkle, Michela Traglia, Terho Lehtimäki, Olli T. Raitakari, Andrew D. Johnson, Christopher Newton-Cheh, Morris J. Brown, Anna F. Dominiczak, Peter J. Sever, Neil Poulter, John C. Chambers, Roberto Elosua, David Siscovick, Tõnu Esko, Andres Metspalu, Rona J. Strawbridge, Markku Laakso, Anders Hamsten, Jouke-Jan Hottenga, Eco de Geus, Andrew D. Morris, Colin NA Palmer, Ilja M Nolte, Yuri Milaneschi, Jonathan Marten, Alan Wright, Eleftheria Zeggini, Joanna MM Howson, Christopher J. O’Donnell, Tim Spector, Mike A. Nalls, Eleanor M. Simonsick, Yongmei Liu, Cornelia M. van Duijn, Adam S. .Butterworth, John N. Danesh, Cristina Menni, Nicholas J. Wareham, Kay-Tee Khaw, Yan V. Sun, Peter WF Wilson, Kelly Cho, Peter M. Visscher, Joshua C. Denny, Million Veteran Program, Lifelines Cohort Study , CHARGE Consortium, ICBP Consortium, Daniel Levy, Todd L. Edwards, Patricia B. Munroe, Harold Snieder, and Helen R. Warren, 30 Apr. 2024, Genetics of nature.
DOI: 10.1038/s41588-024-01714-w

The project was led by NHGRI researchers in collaboration with Queen Mary University of London, Vanderbilt University Medical Center, Nashville, Tenn., the University of Groningen in the Netherlands, and other institutions, as part of the International Blood Pressure Consortium. More than 140 researchers from more than 100 universities, institutes and government agencies contributed to this international study.