Genetics and stem cells

Genes for high blood pressure

“Scientists have pinpointed a clutch of common genes that can lead to high blood pressure,” the Daily Mail reported. It said that up to half the population carries the genes, each of which has only a small effect, but which together could raise the risk of heart attack by more than a fifth and stroke by more than a third. The finding paves the way for new treatments.

This study compared 2.5 million genetic variants from 34,000 people of European ancestry and found eight that had a statistically significant association with blood pressure. The researchers then checked these genetic regions in a further 90,000 white European people and 12,000 people of South Asian descent, and also cross-referenced the findings with data from another study.

Overall, this study clarifies the strength of the link between eight gene variants and blood pressure. More studies that show exactly how these variants influence blood pressure and whether they can be targeted for treatment are needed.

Where did the story come from?

This large international study had many contributors from around the world. The list of authors was led by Dr Christopher Newton-Cheh from the Massachusetts General Hospital in Boston, USA. The study was funded by international research grants. It was published in the peer-reviewed science journal Nature .

What kind of scientific study was this?

This was a genome-wide association study. Its aim was to identify any genetic variations in the human genetic code (genome) that are associated with elevated blood pressure or hypertension. The researchers say that although elevated blood pressure is a common, heritable cause of cardiovascular disease, it has proven difficult to identify the common genetic variants that influence blood pressure.

Part of this analysis involved comparing the genetic code of people with hypertension with that of people with normal blood pressure (controls). After genotyping each participant, the data on the genetic markers was analysed for the closest links to blood pressure.

The researchers looked for single-nucleotide polymorphisms (SNPs). These small genetic variations are of particular interest to researchers as SNPs found within a coding sequence can alter the biological function of a protein. They identified those SNPs that were most often seen in people with elevated blood pressure and then looked for this relationship in the datasets of other studies.

The researchers conducted a meta-analysis of 17 separate genome-wide association studies from across Europe and the US. These had data on the SNPs from individuals of European descent. After excluding people over 70 years of age and those with diabetes or coronary heart disease, the researchers were left with 34,433 individuals for analysis. The meta-analysis produced 12 SNPs with strong, statistically-significant associations with blood pressure.

The researchers then assessed 13 studies with 71,225 individuals of European descent, and a study with 12,889 individuals of Indian–Asian ancestry to see whether these SNPs were also linked with blood pressure.

They also looked at 20 SNPs (10 systolic blood pressure (SBP), 10 diastolic blood pressure (DBP)) for a further analysis in 29,136 individuals of European descent using data from a group known as the CHARGE consortium.

What were the results of the study?

Across all studies, the researchers identified associations between systolic or diastolic blood pressure and common variants (SNPs) in eight regions near the genes known as CYP17A1, CYP1A2, FGF5, SH2B3, MTHFR, c10orf107, ZNF652  and PLCD3. These were all statistically significant associations. All the variants were associated with blood pressure measured on a continuous scale and also with hypertension defined by the cut-off of 140/90.

What interpretations did the researchers draw from these results?

The researchers conclude that the associations they found between common variants and blood pressure or hypertension offer insights into how blood pressure may be regulated. This may lead to new targets for interventions to prevent cardiovascular disease.

They caution that the effect of these genes on blood pressure is modest and that this study may have been too small or had limited power to detect such effects. They say that “it is likely that many more common variants exist with weak effects upon blood pressure”.

What does the NHS Knowledge Service make of this study?

This is an important study and these eight gene variants are among the first confirmed to be associated with blood pressure. How much the variability in blood pressure between individuals is determined by these genes is still to be determined. Some points to consider:

  • The researchers say that each association explains only a very small proportion of the total differences in SBP or DBP (approximately 1 mm Hg SBP or 0.5 mm Hg DBP) per allele, or variation.
  • These variants together have a combined effect on blood pressure, which may be more meaningful for a population rather than an individual. For example, the researchers estimate that a 2 mm Hg lower SBP, across the range of observed values, has been estimated to translate into 6% less stroke and 5% less coronary heart disease.
  • The specific genetic locations that were identified by this study may not necessarily be the ones that are having an effect, but could just lie in the same area in the genetic code as ones that are doing this. The researchers say that it could be any of the genes in the area and further mapping and re-sequencing will be required to refine each “association signal” and to identify likely causal genetic variants that could be studied further in humans and in animal models.

Overall, this important study clarified the strength of the link between eight gene variants and blood pressure. More studies are required to clarify how these variants influence blood pressure and if they can be targeted for treatment and prevention of heart disease or stroke.

NHS Attribution