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Study of one million people leads to major advance in blood pressure genetics

17 Sep 2018

Over 500 new gene regions that influence people’s blood pressure have been discovered in the largest global genetic study of blood pressure to date.

Involving more than one million participants, the results more than triple the number of blood pressure gene regions to over 1,000 and means that almost a third of the estimated heritability for blood pressure is now explained.

The study, led by Queen Mary University of London (QMUL) and Imperial College London, also reports a strong role of these genes, not only in blood vessels, but also within the adrenal glands above the kidney, and in body fat. The full findings were published in the journal Nature Genetics

The research was co-funded by the MRC, along with the National Institute for Health Research (NIHR) and the British Heart Foundation.

High blood pressure is a major risk factor for stroke and heart disease and was responsible for an estimated 7.8 million deaths worldwide in 2015. While lifestyle risk factors are relatively well-known and include obesity, smoking, alcohol and high salt-intake, high blood pressure is also highly heritable through genetics.

Prior to this study however, the genetic architecture of blood pressure had not been well understood.

Professor Mark Caulfield, from QMUL and Director of the NIHR Barts Biomedical Research Centre, said: “This is the most major advance in blood pressure genetics to date. We now know that there are over 1,000 genetic signals which influence our blood pressure. This provides us with many new insights into how our bodies regulate blood pressure, and has revealed several new opportunities for future drug development.

“With this information, we could calculate a person’s genetic risk score for high blood pressure in later life. Taking a precision medicine approach, doctors could target early lifestyle interventions to those with a high genetic risk, such as losing weight, reducing alcohol consumption and increasing exercise.”

The team included a large number of international researchers led by the NIHR Barts Biomedical Research Centre, a joint partnership between QMUL and Barts Health NHS Trust, and Imperial College London. They analysed the DNA of more than one million people, including almost 500,000 from the UK Biobank cohort, and cross-referenced the genetic information with their blood pressure data.

UK Biobank, also part-funded by the MRC, is one of the world’s largest health studies worldwide. It includes extensive information on demographic and lifestyle factors, and the genetic make-up of the 500,000 men and women enrolled in the study.

By comparing the group with the highest genetic risk of high blood pressure with those in the lowest risk group, the team were able to calculate that all the genetic variants were associated with having around a 13 mm Hg higher blood pressure, having 3.34 times the odds for increased risk of hypertension and 1.52 times the odds for increased risk of poor cardiovascular outcomes.

Dr Ivan Pavlov, Programme Manager for Systems Medicine at the MRC, said: “By identifying genes that are associated with several pathologies, the study not only advances our understanding of the high blood pressure genetics, but also reveals potential biological pathways underlying multi-morbidity – when the patient suffers from two or more long-term health conditions. Multi-morbidity is a global challenge, which presents a significant burden for patients and the healthcare system.

“To advance research in this area MRC is currently running a funding call, together with the NIHR, that will support studies aimed at understanding factors that determine disease clustering.”

The study indicates some potential new targets for drug development and suggests that some drugs prescribed for other diseases could be repurposed for treating hypertension. For example, one of the newly discovered gene regions is targeted by the type 2 diabetes drug canagliflozin. Repurposing drugs already known to be safe could be a quick and cost-effective way to treat patients who show resistance or intolerance to current therapies.

This paper is available on Europe PMC.

Categories

  • Categories: Research
  • Health categories: Cardiovascular, Stroke, Generic, Other
  • Locations: London
  • Type: News article, Success story