The new study also found three new genes that appear to have up to twice the effect on blood pressure as previously known genes.
Medical experts define high blood pressure as having a systolic/diastolic blood pressure reading of 140/90 mmHg or higher. They use this threshold because patients experience benefits when they bring their blood pressure below it.
Also, blood pressure levels are known to be positively and continuously related to cardiovascular risk, even below the threshold 140/90 mmHg.
High blood pressure is thought to be responsible for a larger proportion of global disease burden and premature mortality than any other disease risk factor.
According to estimates from the World Health Organization (WHO), every year, high blood pressure causes 7.5 million deaths - about 12.8 percent of all deaths - worldwide.
In 2008 - the most recent year for global data - the worldwide prevalence of high blood pressure in adults aged 25 and over was 40 percent. Rates in Africa were higher, at 45 percent, and in high income countries they were lower, at 35 percent.
Current genetic knowledge on hypertension is limited
Yet, despite the enormous global health burden of high blood pressure, knowledge on the underlying genetics is limited, note the authors of the new study, published in Nature Genetics.
- In the United States, around 1 in 3 adults have high blood pressure
- High blood pressure costs the American economy around $46 billion a year
- High blood pressure is a primary or contributing cause of 1,000 deaths in the U.S. every day.
The research team - led by Queen Mary University of London (QMUL) and the University of Cambridge, both in the United Kingdom - comprised 200 investigators from across 15 countries.
Using genetic data and medical records of over 347,000 individuals from the U.K., Denmark, Sweden, Norway, Finland, Estonia, the U.S., Pakistan, and Bangladesh, they discovered 31 new gene regions linked with blood pressure.
The study participants included healthy people and also people with diabetes, coronary artery disease and hypertension.
The discovery includes DNA alterations in three genes whose effect on blood pressure in the population is bigger than that seen in previously discovered genes. The authors note their findings will improve understanding of the causes of high blood pressure and may lead to new targets for treatment.
The reason the three genes were not known about before is likely to be because of the huge, unprecedented scale of the new study. The genes are not common, and to find them in the population with any level of confidence, you need to include large numbers of participants in the analysis.
Map pathways and highlight treatment targets
One of the researchers, Patricia Munroe, is a professor at QMUL, and her research focuses on clarifying the genetic and molecular basis of hypertension. She says finding more genetic regions linked to high blood pressure means they can now begin to map the biological pathways of the disease and highlight points in them that might be targets for treatment. She notes:
"This could even reveal drugs that are already out there but may now potentially be used to treat hypertension."
One of the three new genes with a strong effect on blood pressure is called RBM47 - it codes for a protein that modifies RNA. Another, called RRAS, is involved in cell cycle processes, and the third, COL21A1, is involved in collagen formation in many tissues.
RRAS has previously been associated with a heart abnormality called Noonan syndrome, and COL21A1 affects tissue in the heart and aorta. Both genes are also involved in blood vessel remodeling, which is important for blood pressure.
The study also uncovers a DNA change in a molecule called ENPEP, whose protein regulates the dilation and constriction of blood vessels, which directly affects blood pressure. The researchers suggest the gene region is a potential target for treatment.
"This study has increased the number of genes implicated in control of blood pressure to almost 100 and, in the process, has also identified three genes that have larger effects on blood pressure than previously found."
Prof. Jeremy Pearson, associate medical director, British Heart Foundation