‘Causal’ blood pressure genes found in the human kidney – The University of Manchester

An international team of scientists led by The University of Manchester have discovered 179 kidney genes responsible for high blood pressure.

High blood pressure, known as silent killer, is one of the most common human diseases and remains the key risk factor for strokes and heart attacks.

High blood pressure - orhypertension- runs in families but the exact mechanisms through which genes influence individuals predisposition to hypertension is not clear.

The discoveries published in Nature Genetics, one of the worlds leading journals, shed new light on our understanding of genetic predisposition to high blood pressure.

The study, supported primarily by the British Heart Foundation and Kidney Research UK, was possible through access to huge datasets of human DNA and RNA from possibly the worlds largest repository of human kidney tissue-based omics.

The team led by Professor Maciej Tomaszewski at The University of Manchester characterised how information inherited in DNA translates into genetic predisposition to high blood through changes in activity of certain kidney genes.

These studies included comprehensive analyses conducted at various molecular levels of kidney tissue combining together DNA, RNA and other layers from the same set of kidney tissue samples.

They also used a statistical method - called Mendelian randomisation to screen for evidence of causal associations between thousands of variables and millions of genetic variants using the high-performance computing resources hosted at the University of Manchester.

Around 80 per cent of 179 genes discovered by the team have never before been associated with high blood pressure before. Some of these genes can be targeted by existing medicines creating new opportunities to treat high blood pressure.

Principal Investigator Maciej Tomaszewski, Professor of Cardiovascular Medicine and University of Manchester and a Consultant Physician said: Hypertension is a key driver of coronary heart disease and stroke and the single most important cause of disability and premature death worldwide.

Yet, our understanding of the role of genes in development of this condition has been incomplete.

Professor Tomaszewski is also a member of Manchester Academic Health Science Centre (MAHSC), a partnership between academia and NHS organisations in Greater Manchester to drive health research, improve health education and transform patient care.

Professor Fadi J Charchar, a senior author from Federation University, added: Our studies filled an important gap in our knowledge through uncovering new genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to genetic regulation of blood pressure and inherited susceptibility to hypertension.

Professor Andrew Morris, from The University of Manchester, commented: Through our unparalleled access to the kidney tissue resource, we provide evidence for the role of the kidney as the mediator of common genetic effects on blood pressure and a potentially causal role of blood pressure in the development of renal disease.

First author: Dr James Eales from The University of Manchester said: By explaining the molecular mechanisms of hypertension embedded in the kidney, our study will ultimately lead to advancements in patient-centred diagnostic accuracy in hypertension.

It will also lead to new targeted strategies to lowering blood pressure, thereby accelerating progress in precision medicine.

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'Causal' blood pressure genes found in the human kidney - The University of Manchester