Researchers have identified more than 2,000 genetic signals linked to blood pressure in a study of more than 1 million people

A major study led by Queen Mary University of London reveals the most detailed picture yet of genetic contributions to blood pressure. The findings lead to improvements in polygenic risk scores, which will better estimate blood pressure and the risk of high blood pressure.

Researchers led by Queen Mary University of London have discovered more than a hundred new regions of the human genome, also known as genomic loci, that appear to influence a person’s blood pressure.

In total, more than 2,000 independent genetic signals are now reported, demonstrating that blood pressure is a highly complex trait influenced by thousands of different genetic variants.

The research, published Tuesday in the journal Nature Geneticsis one of the largest genomic studies of blood pressure to date, including data from more than 1 million people and laying the groundwork for researchers to better understand how blood pressure is regulated.

To understand the genetics of blood pressure, researchers combined four large datasets from genome-wide association studies (GWAS) on blood pressure and hypertension. After analyzing the data, they discovered more than 2,000 genomic loci linked to blood pressure, including 113 new regions.

The analyzes also implicated hundreds of previously unreported genes that affect blood pressure.

Such information could indicate new potential drug targets and contribute to the advancement of 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 combine the effects of all genetic variants together to indicate blood pressure and high blood pressure risk.

For example, these risk scores show that people with the highest genetic risk have mean systolic blood pressure levels that are ~17 mmHg higher than those with the lowest genetic risk and a 7-fold increased risk of hypertension .

Therefore, these polygenic risk scores can discriminate between patients according to their risk of hypertension and reveal clinically significant differences in blood pressure.

“We discovered a much larger proportion of the genetic contribution to blood pressure than previously known,” Helen Warren, senior lecturer in statistical genetics at University College London and one of the lead authors of the study, said in a university statement.

The team made the polygenic risk score data available to the public.

“There are many different potential applications of genetic risk scores, so it will be interesting to see how our blood pressure scores can be used to address more clinically relevant questions in the future,” she said.

The large-scale study was based on more than 18 years of blood pressure GWAS research. The results provide new resources for understanding biological mechanisms and, importantly, new polygenic risk scores for the early identification and stratification of people at risk of cardiovascular disease, says Patricia Munroe, professor of molecular medicine at University College London, and lead author of the paper. .

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 widely applicable in routine medical care.

While the data collected came primarily from people of European ancestry (due to the limited availability of diverse data sets when the study was started), the researchers found that the polygenic risk scores were also applicable to people of African ancestry, which have previously been underrepresented in genetic studies.

This finding regarding African ancestry was confirmed by analysis of data from the National Institutes of Health (NIH) “All of Us” research program in the United States, which aims to create one of the largest biomedical data resources and accelerating research to improve human health.

An estimated 30% of adults in the UK have high blood pressure, known as hypertension.

High blood pressure is often hereditary, meaning there is a genetic component to the development of 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 affect the heart and blood vessels throughout the body, increasing a person’s risk of heart disease, kidney disease, stroke, and other conditions.

The study combined previously published genetic data from UK Biobank, a large-scale biomedical database and research resource containing genetic and health information from half a million UK participants (N~450,000 people); International Blood Pressure Group (N~300,000 people combined from 77 different cohort studies); and the United States Department of Veterans Affairs Million Veteran Program (N~220,000 individuals), with new data from Vanderbilt University Medical Center’s BioVU biorepository (N~50,000 individuals).