More than 30% of adults globally suffer from hypertension, a major controllable risk factor for cardiovascular disease and mortality. Hypertension is characterized by either high systolic blood pressure (SBP) and, or high diastolic blood pressure (DBP) levels (1✔ ✔Trusted Source
Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
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Blood pressure (BP) demonstrates a strong heritability, with numerous genome-wide association studies (GWAS) emphasizing its intricate structure and the effect of multiple genes.
A major progress has been achieved by the scientists in a study at the Queen Mary University of London, in comprehending the genetic elements that impact blood pressure. This study has been published in the journal Nature Genetics by researchers led by Queen Mary University of London and supported by the National Institute for Health and Care Research (NIHR) to understand how blood pressure is influenced by the genetic traits.
The study is one of the most extensive genomic studies on blood pressure to date. It incorporates information from more than 1 million people, providing a foundation for scientists to enhance their comprehension of how blood pressure is controlled.
The results have contributed to enhanced polygenic risk scores (PRSs), resulting in more accurate predictions of blood pressure levels and hypertension risk.
The researchers identified more than a hundred new regions of the human genome, also known as genomic loci, that seem to impact the individual’s blood pressure. A total of over 2,000 independent genetic signals associated with blood pressure had been identified, showing that blood pressure is a highly intricate characteristic influenced by numerous genetic variants.
Study Details and Outcome
The researchers integrated four extensive datasets from genome-wide association studies (GWAS) of blood pressure and hypertension to gain insights into the genetics of blood pressure. Upon detailed analysis of the data, they identified more than 2,000 genomic loci associated with blood pressure, revealing 113 novel regions. Furthermore, the analyses highlighted numerous previously unidentified genes that influence blood pressure. These findings could lead to the identification of new drug targets and contribute to the progress of precision medicine for the early identification and prevention of hypertension.
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The researchers utilized these analyses to compute polygenic risk scores, which integrate the impacts of all genetic variations, to forecast blood pressure and hypertension risk. In particular, these scores indicate that individuals with the highest genetic risk exhibit average systolic blood pressure levels approximately 17 mmHg higher than those with the lowest genetic risk, along with a 7-fold rise in hypertension risk. Consequently, these polygenic risk scores are capable of distinguishing between patients based on their risk of hypertension and expose significant clinical variances in blood pressure.
Helen Warren, Senior Lecturer in Statistical Genetics at Queen Mary University of London and senior last author of the study said, “We have now revealed a much larger proportion of the genetic contribution of blood pressure than was previously known,”. Warren added, “We are making our polygenic risk scores data publicly available. There are many different potential applications of genetic risk scores, so it will be exciting to see how our blood pressure scores can be used to address more clinically relevant questions in the future.”
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Patricia Munroe, Professor of Molecular Medicine at Queen Mary University of London, and another senior author of the paper, said, “This large study builds on over 18 years of blood pressure GWAS research. Our results provide new resources for understanding biological mechanisms and importantly new polygenic risk scores for early identification and stratification of people at risk for cardiovascular diseases”.
Polygenic risk scores have the probability to be a valuable tool in precision medicine. However, a wider range of genomic data is required for them to be widely applicable in routine healthcare. Initially, the collected data focused on individuals of European descent, due to the limited availability of diverse datasets at the beginning of the study. Subsequently, the researchers discovered that the polygenic risk scores could also be utilized for individuals of African descent, a group that has historically been underrepresented in genetic research. This finding was verified by analyzing data from the National Institute of Health’s (NIH) All of Us Research Program in the United States, which aims to establish one of the largest biomedical data repositories and expedite research efforts to enhance human health.
Approximately 30% of adults residing in the United Kingdom are affected by high blood pressure, medically referred to as hypertension. This condition often has a hereditary aspect, indicating that genetics play a role in its development, alongside environmental factors like consuming excessive amounts of salt, leading a sedentary lifestyle, smoking, and experiencing stress. The constant elevated blood pressure levels can result in detrimental effects on the heart and blood vessels, thereby amplifying the individual’s susceptibility to heart disease, kidney disease, stroke, and various other health complications.
The research integrated existing genetic information from the UK Biobank, a comprehensive biomedical database with data on genetics and health from around 450,000 UK individuals; the International Consortium for Blood Pressure, which pooled data from 300,000 individuals across 77 cohort studies; and the Million Veteran Program by the U.S. Department of Veterans Affairs, which included information from 220,000 individuals. Furthermore, data from Vanderbilt University Medical Center’s BioVU biorepository, involving 50,000 individuals, was also included in the study.
This comprehensive study encompassing more than one million European individuals led to the identification of more than 2000 BP signals from known and new loci (locations). This study helped the creation of PRSs that captured substantial interindividual variation in BP traits. The PRSs are accessible to the research community worldwide and can be used for further investigations on BP.
Reference:
- Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits – (https://pubmed.ncbi.nlm.nih.gov/38689001/)
Source-Eurekalert
