Unlocking the genetic mysteries of blood pressure: new research identifies potential causal genes and drug targets
Scientists from Queen Mary University of London and Universities of Manchester, Zaragoza and Oxford, have revealed the genetic underpinnings of blood pressure regulation, offering hope for more effective treatments and preventative measures for hypertension.
The study was supported by the National Institute for Health and Care Research (NIHR) Manchester and Barts Biomedical Research Centres (BRCs) and the European Union, and published in The American Journal of Human Genetics. The findings represent a critical step towards identifying candidate genes for blood pressure regulation.
Hypertension, or high blood pressure, is a global health concern with a profound impact on public health. The condition affects over one billion people worldwide and is a major risk factor for cardiovascular disease. It is widely recognised that genetics contributes up to 50% of the variability in blood pressure between people, yet the specific genes responsible and the underlying biological processes have yet to be characterised. In this study, scientists set out to tackle the knowledge gap by using genetic data available through large genome-wide association studies (GWAS).
By searching across the whole genome, GWAS can identify sets of DNA variants that influence blood pressure. However, there have been limited follow-up studies to understand the specific genes that “interpret” the DNA code from these variants and the biological processes in the human body through which these genes impact on blood pressure regulation.
The research team, led by experts in genetics and bioinformatics, employed innovative computational approaches that combined GWAS with state-of-the-art data from the latest studies that aim to determine how DNA variants change the way genes operate, and the organs and tissues in the body in which these changes take place. Understanding these genes and processes is essential because drugs can be developed or repurposed to “correct” these changes that lead to high blood pressure.
With this comprehensive approach, the researchers identified 1,850 sets of DNA variants that influence at least one measure of blood pressure (systolic, diastolic, and pulse), of which 532 sets contribute to regulation of all three.
In total, the study consolidated evidence for 436 candidate genes that influence blood pressure, paving the way for more detailed future studies to fully understand how these genes and biological processes might lead to hypertension . Significantly, this research also unearthed several new drug targets for hypertension, with the gene PDE3A standing out as a particularly promising candidate.
Professor Andrew Morris, Professor of Statistical Genetics at The University of Manchester and Rheumatic and Musculoskeletal Diseases Co-Theme Lead at Manchester BRC said: “Our study has highlighted that hundreds of sets of DNA variants influence blood pressure, and these variants work together through complex biological processes in the body that together lead to the development of hypertension.”
Patricia Munroe, Professor of Molecular Medicine at Queen Mary University of London and Precision Genomic Medicine Co-Theme lead at Barts BRC said: “Our results provide a crucial foundation for understanding how DNA variants influence blood pressure in the general population. They have potential to enable new preventative and therapeutic opportunities for hypertension with wider implications for cardiovascular health.”