Over 500 genes linked with high blood pressure

The results of a study that reports are dubbing “one of the biggest breakthroughs yet in blood pressure genetics” have just been released.
25 September 2018

Interview with 

Mark Caulfield, Queen Mary University of London


Blood pressure check


The results of a study that reports are dubbing “one of the biggest breakthroughs yet in blood pressure genetics” have just been released. Scientists at Queen Mary University of London have looked at the genetic signatures of more than a million people and married their genes with their lifestyle factors and their blood pressures. The result is the identification of hundreds of new genes linked to high blood pressure which should highlight new ways to predict who’s at risk, reveal new drug treatments and even flag up some simple home remedies that are surprisingly effective. Chris Smith spoke to Mark Caulfield, who led the study…

Mark - We studied over one million people, most of whom are of white European ancestry. The main component of the study was The United Kingdom Biobank, which is the jewel in Britain’s crown in terms of understanding the genetic basis of disease - that’s half a million people. Then we combined it with other studies from across the world and that allowed us to reach the number of one million. And it is the size of the study and the precision of the analysis that’s allowed us to find these loci for blood pressure.

Chris - And when you look at these genetic regions that seem to be important for blood pressure, what emerges and why does this matter? How does this affect our ability to diagnose, manage, and better manage high blood pressure?

Mark - Actually measuring the blood pressure this way would not be efficient. But what this does do, is it gives us new biological insights into why some people’s blood pressure is higher than others. The other correlations we found in the project were with certain treatments so, for example, we found evidence that a fairly new diabetic treatment, which is very effective at lowering blood sugar that has also been shown to reduce adverse heart disease and stroke. The target for that drug is a gene for blood pressure. Could we take that medicine and use it more often in people with high blood pressure and diabetes so effectively treating two things at once? So this is about understanding how we can get new insights into the biology that will allow us to develop new therapies or approaches that will improve the care of people across the world with this burgeoning epidemic of high blood pressure.

Chris - But will it actually achieve that lofty goal though, Mark? Because I put it to you, we’ve known about some of the genes that lead to obesity and overweight for a long time but we’ve got record numbers of people on Earth with problems related to carrying too much weight. So at what point are we going to see this magic sort of translation of the genetic information that you’re flushing out with amazing studies like this one into a pill that I can take that means I’m not going to have the same heart attack and stroke risk?

Mark - I can give you some examples. In our own work at my institution we’ve been working on a pathway that we discovered a few years ago and that involves a chemical in our body call nitric oxide. When you drink beetroot juice, just 250 mls of beetroot juice, which contains very rich concentrations of a chemical called nitrate which is converted in our bodies to this nitric oxide and opens up blood vessels and lowers blood pressure.

We’ve shown now in convincing studies in people with high blood pressure that this can be taken as effectively, a form of lifestyle treatment. So you can go into supermarkets as a result of this research and buy that for yourself. Why this is popular with patients is that patients do like the idea of a lifestyle modification as opposed to just a pure chemical tablet.

The other areas where this has been particularly helpful is observations made in high cholesterol which can run in families have allowed us to invent an injection that you can give once every couple of weeks, or once a month, and it profoundly lowers cholesterol. So it’s not simply about discovering new things that don’t translate into the clinic.

Chris - So if I take the average person in the population with high blood pressure, what fraction of people can I explain their high blood pressure, on the basis of the genes that your study, and the ones we already knew about, tell us?

Mark - An important feature of this study, which makes this an incredibly good question, we estimate from this study that we’ve explained 27 percent, now, with all of the known findings, and the new ones we report here of the influences on blood pressure.

Chris - That said though, Mark, that still leaves two thirds of the field open, doesn’t it, unaccounted for? Where is that two thirds to three quarters of the cause of blood pressure then if you can only account with a huge study like this for 27 percent of it?

Mark - I think probably the best way to describe this is, there may be many routes for people’s blood pressure to be elevated. That means that the studies being done to date, mostly we’ve measured the common molecular signatures and not the rare ones. Now with whole genome sequencing and other technologies we’re able to read the entire genetic code of a human and therefore we get the entire blueprint for life, and then we can measure the rare variations that could be contributing significantly. So I believe we will gain access within the next few years to the remaining missing heritability for blood pressure.


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