Like many medical conditions, high blood pressure is the result of some combination of environmental risk factors — like lack of exercise, smoking and obesity — and genes. Now an international research consortium publishing in Nature has helped shed light on the genetic piece of the puzzle, identifying 29 genetic variations across 28 regions of the genome that influence risk of hypertension.
The study was based on an analysis of data on more than 200,000 people of European descent. Hundreds of scientists from 24 countries collaborated to identify the 29 genetic variations — 16 of which were identified for the first time — that were associated with blood pressure. Six of the new variations were found in genes that researchers already knew were linked with blood pressure; the other 10 were found in unexpected regions of the genome, offering new clues to how blood pressure is controlled.
The variants are common — each one exists in at least 5% of people. Each individual variant was associated with only a tiny increase in risk of hypertension, but people with multiple variants had higher risks. So the researchers developed a genetic risk score based on combinations of variants: people with more variants and a higher score had a correspondingly higher risk of high blood pressure; people with few variants and a low score had a lower risk of hypertension.
Indeed, compared with people in the bottom 10%, those in the top 10% of genetic risk scores had 5.8 mm Hg and 3.7 mm Hg higher systolic and diastolic blood pressure readings, respectively. (The first number refers to blood pressure when the heart is pumping; the second number refers to blood pressure between beats.)
Risk of hypertension also increased with the risk score: 29% of people in the highest risk group at hypertension, compared with 16% of those in the lowest risk group.
To further test the association between the genetic variants and blood pressure, the researchers continued their analysis more than 70,000 people of East Asian, South Asian or African ancestries. They found that the genetic risk score and many of the same genetic variants were associated with high blood pressure in these populations too.
In a related study published in Nature Genetics, the same scientific team identified an additional six regions of the genome, in more than 120,000 people, where variants were associated with two other measurements of blood pressure: pulse pressure (the difference between systolic and diastolic blood pressure) and arterial pressure (a weighted average of systolic and diastolic pressure). Both of these measures also linked with high blood pressure and heart disease.
“Your blood pressure is a function of these genes we just identified as well as perhaps a hundred others we haven’t found yet,” said study author Dr. Aravinda Chakravarti, a professor of medicine, pediatrics and molecular biology and genetics at the Johns Hopkins McKusick-Nathans Institute of Genetic Medicine, in a statement. “By revealing the genetic architecture of blood pressure, both studies will help us to understand the biology of cardiovascular diseases and stroke, and, eventually, may lead to better therapies.”