NIH-led study finds genetic markers that explain up to 12% of the differences between two people’s blood pressure.
National Institutes of Health researchers and collaborators have discovered over 100 new regions of the human genome, also known as genomic loci, that appear to influence a person’s blood pressure. Results of the study also point to several specific genomic loci that may be relevant to iron metabolism and a type of cellular receptor known as adrenergic receptors.
The study, published in Nature Genetics, is one of the largest such genomic studies of blood pressure to date, including data from over 1 million participants and laying the groundwork for researchers to better understand how blood pressure is regulated. Such insights could point to potential new drug targets.
“Our study helps explain a much larger proportion of the differences between two people’s blood pressure than was previously known,” said first author Jacob Keaton, PhD. “Our study found additional genomic locations that together explain a much larger part of the genetic differences in people’s blood pressure. Knowing a person’s risk for developing hypertension could lead to tailored treatments, which are more likely to be effective.”
Hypertension often runs in families, meaning that there is a genetic component to developing the condition in addition to environmental contributions such as a high-salt diet, lack of exercise, smoking and stress.
To understand the genetics of blood pressure, the researchers combined four large datasets from genome-wide association studies of blood pressure and hypertension. After analysing the data, they found over 2000 genomic loci linked to blood pressure, including 113 new regions. Among the newly discovered genomic loci, several reside in genes that play a role in iron metabolism, confirming previous reports that high levels of accumulated iron can contribute to cardiovascular disease.
The researchers also confirmed the association between variants in the ADRA1A gene and blood pressure. ADRA1A encodes a type of cell receptor, called an adrenergic receptor, that is currently a target for blood pressure medication, suggesting that other genomic variants discovered in the study may also have the potential to be drug targets to alter blood pressure.
“This study shows that these big genome-wide association studies have clinical relevance for finding new drug targets and are needed to discover more drug targets as we go forward,” said Dr Keaton.
From these analyses, the researchers were able to calculate a polygenic risk score, which combines the effects of all genomic variants together to predict blood pressure and risk for hypertension. These risk scores consider which genomic variants confer risk for hypertension and reveal clinically meaningful differences between people’s blood pressure.
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, the polygenic risk scores were also applicable to people of African ancestry.
Source: National Institutes of Health
