Scientists report over 2,000 genetic signals linked to blood pressure

UMCG researchers and collaborators have discovered over a hundred new regions of the human genome, also known as genomic loci, that appear to influence a person’s blood pressure. In total, over 2,000 independent genetic signals for blood pressure are now reported, demonstrating that blood pressure is a highly complex trait, influenced by thousands of different genetic variants.

The study, published in Nature Genetics, is one of the largest such genomic study of blood pressure to date, including data from over 1 million individuals and laying the groundwork for researchers to better understand how blood pressure is regulated.  

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 over 2,000 genomic loci linked to blood pressure, including 113 new regions. The analyses also implicated hundreds of previously unreported genes that affect blood pressure. Such insights could point to potential new drug targets, and help to advance precision medicine in the early detection and prevention of hypertension (high blood pressure). 

From these analyses, the researchers were able to calculate polygenic risk scores, which combines the effects of all genetic variants together, in order to predict blood pressure and risk for hypertension in the Lifelines study. For example, these risk scores show that individuals with highest genetic risk have mean systolic blood pressure levels which are ~17 mmHg higher than those with lowest genetic risk, and a 7-fold increased risk of hypertension. Therefore these polygenic risk scores can discriminate patients according to their hypertension risk, and reveal clinically meaningful differences in blood pressure. 

“We have now revealed a much larger proportion of the genetic contribution of blood pressure than was previously known,” says Harold Snieder, Professor of Genetic Epidemiology at the University Medical Center Groningen, and one of the senior authors of the study.  “We are making our new polygenic risk scores publicly available, which will improve early identification and stratification of people at risk for cardiovascular diseases.” 

“Our results provide new resources for understanding biological mechanisms pointing to potential new drug targets for high blood pressure treatment” says Ahmad Vaez, Senior Bioinformatician at the University Medical Center Groningen and a corresponding author of the paper. “Now is the time to start thinking about incorporating polygenic risk scores in standard of care of hypertension.” 

Polygenic risk scores have potential to serve as a useful tool in precision medicine, but more diverse genomic data is needed for them to be applicable broadly in routine health care. While the collected data was mostly from people of European ancestry (due to limited availability of diverse datasets when the study was started), the researchers found that the polygenic risk scores were also applicable to people of African ancestry, who have previously been underrepresented in genetic studies.  

An estimated 25% of adults in the Netherlands have high blood pressure, known as hypertension. High blood pressure often runs in families, meaning that there is a sizable 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 a person’s risk for heart disease, kidney disease, stroke and other conditions. 

The study combined previously published genetic data from the UK Biobank, (N~450,000 individuals), the International Consortium for Blood Pressure (N~300,000 individuals combined from 77 different cohort studies), and the U.S. Department of Veterans Affairs’ Million Veteran Program (N~220,000 individuals), with new data from Vanderbilt University Medical Center’s biorepository, BioVU (N~50,000 individuals).   

The project was led by researchers at the University Medical Center Groningen in the Netherlands in collaboration with Queen Mary University of London in the UK, the National Human Genome Research Institute and Vanderbilt University Medical Center in the USA, and other institutions, as part of the International Consortium of Blood Pressure. Altogether, over 140 investigators from more than 100 universities, institutes, and government agencies throughout the world contributed to this international study. 

Here you can find the full publication in Nature Genetics.