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Researchers from the National Institutes of Health (NIH) and several global institutions have identified over 100 new regions within the human genome that influence blood pressure, significantly expanding our understanding of the genetic factors involved. The findings, detailed in Nature Genetics emerged from one of the largest genomic studies on blood pressure, incorporating data from more than one million participants.
Genetic Factors and Blood Pressure
The study's large scale allowed for a detailed analysis of how genetic variations contribute to blood pressure regulation. Over 2,000 genomic loci linked to blood pressure were examined, with 113 of these being newly discovered regions. Notably, some of these regions are involved in iron metabolism, reinforcing earlier studies that suggested accumulated iron can impact cardiovascular health.
Jacob Keaton, Ph.D., a staff scientist at the National Human Genome Research Institute (NHGRI) and first author of the study, emphasized the significance of these findings. "Our study helps explain a much larger proportion of the differences between two people’s blood pressure than was previously known," Dr. Keaton explained. He noted that these insights could lead to personalized treatment strategies for hypertension, potentially improving therapeutic efficacy.
Advanced Techniques in Genomic Analysis
To unearth these findings, researchers utilized a comprehensive approach by merging four extensive datasets from genome-wide association studies (GWAS) focused on blood pressure and hypertension. This robust analysis not only pinpointed new genomic loci but also confirmed the role of the ADRA1A gene in blood pressure regulation. ADRA1A, which encodes an adrenergic receptor, is already a target for existing blood pressure medications, suggesting other discovered variants could also serve as new therapeutic targets.
"This study shows that these big genome-wide association studies have clinical relevance for finding new drug targets and are needed to discover more drug targets as we go forward,” Keaton remarked.
The Role of Polygenic Risk Scores in Precision Medicine
A significant outcome of the study was the development of polygenic risk scores, which aggregate the effects of various genetic variants to predict an individual's blood pressure and hypertension risk. These scores are crucial for identifying individuals at higher risk and could be instrumental in tailoring personal medical treatments.
However, the application of these risk scores in diverse populations remains a challenge. The majority of the data used was from individuals of European ancestry, with limited data from other ethnic backgrounds. Despite this, the study also tested these scores in individuals of African ancestry using data from the NIH’s All of Us Research Program, indicating broader applicability.
Global Collaboration and Future Directions
The project was a collaborative effort involving over 140 investigators from more than 100 universities, institutes, and government agencies worldwide, coordinated by NHGRI, Queen Mary University of London, Vanderbilt University Medical Center, the University of Groningen, and other institutions. This international consortium highlights the importance of collaborative research in advancing our understanding of complex health conditions like hypertension.
The discovery of these genomic loci provides a richer map of the genetic architecture of blood pressure regulation, offering potential new pathways for therapeutic intervention. However, as Keaton suggests, further research is essential to translate these genetic insights into effective and precise treatments for hypertension, a condition affecting nearly half of the adult population in the United States.
Original Publication
Keaton, J.M., Kamali, Z., Xie, T. et al. Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits. Nat Genet (2024). https://doi.org/10.1038/s41588-024-01714-w
Genetic Factors and Blood Pressure
The study's large scale allowed for a detailed analysis of how genetic variations contribute to blood pressure regulation. Over 2,000 genomic loci linked to blood pressure were examined, with 113 of these being newly discovered regions. Notably, some of these regions are involved in iron metabolism, reinforcing earlier studies that suggested accumulated iron can impact cardiovascular health.
Jacob Keaton, Ph.D., a staff scientist at the National Human Genome Research Institute (NHGRI) and first author of the study, emphasized the significance of these findings. "Our study helps explain a much larger proportion of the differences between two people’s blood pressure than was previously known," Dr. Keaton explained. He noted that these insights could lead to personalized treatment strategies for hypertension, potentially improving therapeutic efficacy.
Advanced Techniques in Genomic Analysis
To unearth these findings, researchers utilized a comprehensive approach by merging four extensive datasets from genome-wide association studies (GWAS) focused on blood pressure and hypertension. This robust analysis not only pinpointed new genomic loci but also confirmed the role of the ADRA1A gene in blood pressure regulation. ADRA1A, which encodes an adrenergic receptor, is already a target for existing blood pressure medications, suggesting other discovered variants could also serve as new therapeutic targets.
"This study shows that these big genome-wide association studies have clinical relevance for finding new drug targets and are needed to discover more drug targets as we go forward,” Keaton remarked.
The Role of Polygenic Risk Scores in Precision Medicine
A significant outcome of the study was the development of polygenic risk scores, which aggregate the effects of various genetic variants to predict an individual's blood pressure and hypertension risk. These scores are crucial for identifying individuals at higher risk and could be instrumental in tailoring personal medical treatments.
However, the application of these risk scores in diverse populations remains a challenge. The majority of the data used was from individuals of European ancestry, with limited data from other ethnic backgrounds. Despite this, the study also tested these scores in individuals of African ancestry using data from the NIH’s All of Us Research Program, indicating broader applicability.
Global Collaboration and Future Directions
The project was a collaborative effort involving over 140 investigators from more than 100 universities, institutes, and government agencies worldwide, coordinated by NHGRI, Queen Mary University of London, Vanderbilt University Medical Center, the University of Groningen, and other institutions. This international consortium highlights the importance of collaborative research in advancing our understanding of complex health conditions like hypertension.
The discovery of these genomic loci provides a richer map of the genetic architecture of blood pressure regulation, offering potential new pathways for therapeutic intervention. However, as Keaton suggests, further research is essential to translate these genetic insights into effective and precise treatments for hypertension, a condition affecting nearly half of the adult population in the United States.
Original Publication
Keaton, J.M., Kamali, Z., Xie, T. et al. Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits. Nat Genet (2024). https://doi.org/10.1038/s41588-024-01714-w