Genetics underpinning high blood pressure risk identified

Blood pressure regulation and risk of hypertension (high blood pressure) are influenced by over 2000 genomic regions.

Publishing their findings in Nature Genetics, an international team of scientists uncovered 2103 genomic regions, also known as genomic loci, associated with blood pressure, of which 113 were newly described regions. The study, which included data from over one million people, is one of the largest genomic studies of blood pressure. The scientists confirmed the identification of 38 genes with potential as drug targets, including five genes already targeted by other approved drugs.

'Our study helps explain a much larger proportion of the differences between two people's blood pressure than was previously known', said first author, Dr Jacob Keaton, from the National Institutes of Health, Maryland, and Vanderbilt University Medical Centre, Tennessee. 'Our study found additional genomic locations that together explain a much larger part of the genetic differences in people's blood pressure.'

Hypertension can be caused by diet, lifestyle, or medical conditions – such as kidney disease or diabetes – but it can also be inherited. It is estimated that 30 percent of adults in the UK have hypertension.

The researchers combined four blood pressure and hypertension datasets from genome-wide association studies, which included genomic data from 1,028,980 people of European ancestry. Analysing the data, the scientists identified several specific genomic loci that affect blood pressure, which they used to calculate polygenic risk scores.

Polygenic risk scores are developed by combining the small effects of many genetic variants to give an idea of a person's genetic predisposition to a particular disease or trait – in this case, hypertension.

The scientists observed that the ten percent of people with the highest polygenic risk scores had more than a seven-fold increased risk of developing hypertension compared to the ten percent of people with the lowest polygenic risk scores.

'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', said Dr Helen Warren, senior lecturer in statistical genetics at Queen Mary University of London, and joint supervisor of the study.

Most genomic studies are conducted in people of European ancestry, as is the case for this study, which means that the polygenic risk scores may not be applicable to people of other ancestries. Therefore, the researchers tested the polygenic risk scores on 21,843 people of African-American ancestry, from the All-Of-Us research programme, and found that they were also applicable to this population.

Polygenic risk scores could be a potential tool in precision medicine, however, more diverse genomic datasets must be tested before they can be broadly integrated into routine health care.

'Knowing a person's risk for developing hypertension could lead to tailored treatments, which are more likely to be effective,' said Dr Keaton.