New genetic links to blood pressure

Tuesday September 13 2011

“More than 20 new sections of genetic code have been linked to blood pressure,” BBC News has reported. The broadcaster says that until now there has been poor understanding of the genetic element of high blood pressure.

The genetic variations were identified in two large studies conducted by the International Consortium for Blood Pressure Genome-Wide Association Studies, which is a team of international experts committed to understanding the genetics that underlie blood pressure. Their first study examined the genetics of around 200,000 European individuals and identified 29 regions of the DNA where variations in a person’s genetic code may influence their blood pressure. Sixteen of these regions had not been identified in previous studies. In a second study the researchers examined the genetics of 74,000 individuals. They identified four regions of the DNA associated with pulse pressure, which is the difference in pressure in the arteries when the heart is relaxed and contracting, and two with average arterial pressure. Both of these measures are thought to have an influence on cardiovascular disease risk.

These studies are of high scientific value. They further our understanding of how genes may be involved in blood pressure and why high blood pressure may run in families. However, the results do not have any immediate or short-term implications for treatments and it is also likely that there are many further genetic associations left to discover. Whatever role our genes may have, we cannot change our genetic makeup but we can control a number of lifestyle factors that contribute to raised blood pressure. Following a sensible diet and staying active can reduce the risk of high blood pressure and associated health problems.

Where did the story come from?

The BBC news report is based on two research papers on the relationship between genetics and blood pressure that were published in the scientific journals Nature and Nature Genetics . Both have been authored by The International Consortium for Blood Pressure Genome-Wide Association Studies (ICBP-GWAS), which is an extensive network of international researchers from the UK, Europe, US and other countries who aim to understand the genetics that may underlie blood pressure. The study in Nature reports on genetic variants that may be involved in blood pressure and cardiovascular disease based on an analysis of around 200,000 Europeans. The second study, published in Nature Genetics, builds on this analysis by identifying further genetic regions that may be associated with blood pressure.

Several organisations provided funding for these studies, including the US National Institutes of Health and the US National Heart, Lung, and Blood Institute. Various members of the ICBP-GWAS group have declared that they are also members of the CHARGE and Global BPgen research consortia.

The BBC provided balanced coverage of the studies.

What kind of research was this?

These were analyses of genome-wide association studies, which are a type of case-control study. They look for genetic differences between people with a certain characteristic or condition (the cases) and people without the characteristic or condition (the controls). In this instance the researchers were looking at genetic differences between groups of people with raised and normal blood pressure, which could potentially identify genetic factors contributing to high blood pressure.

This is a standard way of investigating the genetic contribution to conditions where multiple genes are likely to be having an effect.

What did the research involve?

Several previous genome-wide association studies are said to have identified regions of the DNA that are associated with diastolic and systolic blood pressure. Diastolic blood pressure, which is the lower figure of a two-figure reading, is  measure of the blood pressure in the arteries while the heart is filling with blood between beats. Systolic blood pressure, the upper figure, is a measure of blood pressure while the heart is contracting and pumping blood into the arteries. A patient with a systolic pressure value of 120 and a diastolic pressure value of 80 would be described as having blood pressure of “120 over 80”.

In Nature , the ICBP-GWAS reports the results of a new analysis of genome-wide association studies that aimed to identify additional regions of the DNA that may have an influence on blood pressure. This study initially looked at data on 69,395 individuals of European ancestry from 29 studies and combined this with an analysis of 133,661 further individuals to examine a total sample of more than 200,000 people.

The study published in Nature Genetics featured an analysis of 35 previous genome-wide association studies covering 74,064 European individuals. It examined genetic associations with pulse pressure, which is the difference between diastolic and systolic figures and a measure of the stiffness or rigidity of the walls of the arteries. It also examined genetic associations with mean arterial pressure, which is an average of systolic and diastolic blood pressure. Both pulse pressure and mean arterial pressure are said to be predictive of hypertension and cardiovascular disease.

What were the basic results?

In the first study the researchers were looking for associations between blood pressure and single nucleotide polymorphisms (SNPs), which are single letter variations in the code found within DNA.

Their analysis of data on 200,000 individuals of European descent identified 29 single nucleotide polymorphisms that were significantly associated with either systolic blood pressure, diastolic blood pressure or both. Sixteen of these 29 SNPs were newly identified by this research and had not previously been associated with blood pressure. Of these 16, six were found to be in regions of the DNA that contain genes already suspected to have a role in the control of blood pressure. The other 10 SNPs did not involve any genes previously thought to have any association with blood pressure and provide possible new clues to the genetic control of blood pressure.

However, as the researchers say, these 16 newly associated variants had only small effects on diastolic and systolic blood pressure (each variant was associated with less than 1.2mmHg difference in blood pressure, and such a small rise would be expected to have limited clinical significance).

When performing further analyses looking at differences relating to gender and BMI they found that the genetic variants seemed to have similar effects in men and women, and in people with different BMIs. They then looked to see whether the blood pressure variants identified in individuals of European ancestry were also associated with blood pressure in individuals of East Asian (529,719 people), South Asian (523,977 people)and African (519,775 people) descent. They found associations between blood pressure and nine of the SNPs in East Asian people, and six SNPs in South Asian people.

The researchers then modelled the cumulative effect of all of the 29 SNPs identified to calculate what they called “a genetic risk score”, which is a measure estimating the total risk of hypertension and related health outcomes that could be attributed to these genetic variations. They found that genetic risk score was significantly associated with high blood pressure (hypertension), clinical history of stroke, coronary artery disease and with having the clinical finding of increased thickness of the wall of the left heart chamber.

In the second paper, in Nature Genetics, the ICBP-GWAS identified new associations between four SNPs and pulse pressure, and between two SNPs and mean arterial pressure. Of the four SNPs associated with pulse pressure they found that three produced opposing effects on systolic and diastolic blood pressure, being associated with both higher diastolic blood pressure and lower systolic blood pressure, or vice versa. They also identified one SNP associated with both pulse pressure and mean arterial pressure, which has also recently been associated with systolic blood pressure in people of East Asian descent.

How did the researchers interpret the results?

The researchers conclude that their findings “provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention”. They also note that their findings also suggest that some of the genetic associations of blood pressure may have different effects on systolic and diastolic blood pressure.


These extensive studies by The International Consortium for Blood Pressure Genome-Wide Association Studies have identified a number of genetic variations associated with blood pressure. The first study has identified 29 regions of the DNA (16 newly identified) where variations in the DNA sequence may have an influence on systolic and diastolic blood pressure. The second study has found four regions of the DNA associated with pulse pressure, two with mean arterial pressure and one region associated with both measures. Pulse pressure and mean arterial pressure are measures related to blood pressure and may have an influence on cardiovascular disease risk.

The studies are of high scientific value in furthering our understanding of how genetics may be involved in blood pressure and why high blood pressure may run in families. However, they do not provide the full answer to the causes of hypertension and do not have any immediate or short-term implications for treatments. It is likely that other regions of the DNA may have a role, and as BBC News reports, “researchers say they have still uncovered only 1% of the genetic contribution to blood pressure”.

While we cannot change the role our genes may play in high blood pressure, genes are not the sole factor governing our blood pressure and there are several risk factors that we can control. Regardless of our genetics, factors such as maintaining a healthy weight, limiting alcohol intake, not smoking, avoiding excess salt and eating a sensible diet can all contribute to lowering blood pressure and the risks of associated health problems.

Analysis by Bazian
Edited by NHS Choices