​​​​​​Photo: Senior researcher Tarunveer Singh Ahluwalia is one of the lead researchers behind the new genetic study of children’s blood pressure and heart rate. He now aims to integrate the genetic data so that doctors and nurses can more easily make individual risk assessments in their daily clinical work.

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High blood pressure is often considered an adult problem. But part of the risk arises much earlier and can be traced back to childhood.

This is shown in a new study published in European Heart Journal, in which researchers – including lead researchers from Steno Diabetes Center Copenhagen – analysed genetic data from more than 28,000 children and adolescents aged 4 to 17 years.

The study is the largest of its kind and identifies eight genetic loci associated with blood pressure in childhood and three associated with heart rate (pulse). It is also the first large-scale genetic study of heart rate in children.

First, the researchers identified genetic variants linked to blood pressure in children. They then used these findings to calculate a genetic risk score (GRS) and compared it with data from more than 450,000 adults in the UK Biobank. The results showed that children with a genetic predisposition to higher blood pressure may have an increased risk of several diseases later in life. The diseases include hypertension, type 2 diabetes, heart attack, heart failure and chronic kidney disease.

The fact that high blood pressure in childhood is linked to disease later in life is not new. What is new is that researchers can now see what lies behind it, explains one of the study’s lead authors, Tarunveer Singh Ahluwalia, senior researcher at the Clinical & Translational Re-search Department, Steno Diabetes Center Copenhagen and an Associate Professor at the Department of Biology (Bioinformatics), University of Copenhagen.

“Clinically, we have long known that higher blood pressure in children is linked to disease later in life. However, our results provide insight into the genes involved and how they might contribute,” says Tarunveer S. Ahluwalia.

A combined measure of disease risk

The study is based on GWAS (Genome Wide Association Study) analyses, a method in which researchers examine millions of small variations in the genome. Each common genetic variant has only a small effect, but together they can be used to calculate a genetic risk score, which is an overall measure of whether a child has a slightly higher or lower predisposition to high blood pressure.

More specifically, the researchers found that presence of these genetic risk markers explained some proportion of the variation in blood pressure and pulse (up to 1.6% and 5.2%, respectively) in children of European ancestry. These findings make it possible to better understand the key biological (genetic) mechanisms involved in blood pressure and pulse regulation and how they are different from non-genetic risk factors like lifestyle and environment.

These findings indicate that genetic markers can provide important insights into disease origins and biological mechanisms. However, on their own, they have limited potential as clinical risk predictors or as a definitive guide to future disease. Therefore, it is not possible to determine a person’s fate in childhood based solely on genetic risk factors, stresses Tarunveer S. Ahluwalia. However, they may make it easier to identify potential vulnerability. 

“Genetics help us understand the underlying mechanisms, but it is only part of the picture. It does not mean that a child will necessarily develop disease. Environment, lifestyle and other factors still play a very large role,” he says.

An overlooked risk in Denmark

In Denmark, the prevalence of high blood pressure is estimated at 2–4% among individuals under the age of 18, corresponding to up to around 46,000 children and adolescents. Globally, the prevalence is around 7% in recent estimates. With increasing rates of childhood obesity, the numbers are rising constantly.

However, blood pressure is typically only measured when there is suspicion of disease, symptoms or known risk factors. As a result, the problem may be more widespread than currently detected.

A group of researchers from Regional Hospital Gødstrup is currently examining 10,000 schoolchildren, and when the results are available next year, they may provide a clearer indication of how many Danish children are living with undiagnosed high blood pressure.

The new study therefore speaks directly to a Danish context in which early detection and pre-vention remain open questions. According to Tarunveer S. Ahluwalia, the perspective is not that all children should undergo genetic testing tomorrow, but that genetic knowledge could, over time, supplement the clinical tools already used in healthcare.

“The key idea is to identify risk earlier in life, rather than reacting only when disease has already developed. In the future, genetic risk scores could become an additional layer on top of the clinical information we already use for individualised or precision treatment, says Tarunveer S. Ahluwalia.”

Steno aims to use genetics to target treatment

At Steno Diabetes Center Copenhagen, researchers are already working to translate genetic knowledge into clinical practice. The goal is to combine genetic risk scores with the tools clinicians already use for risk calculation. At Steno, the approach is referred to as a ‘risk engine’: a screening method based on different types of data that provide clinicians with a more precise picture of an individual patient’s risk.

“Today, we might be using clinical factors such as cholesterol, blood pressure and smoking status for cardio-renal risk estimation. In the future, we would like to supplement these with genetic risk scores to create a more complete and realistic risk profile,” he says.

One of the next steps is to investigate whether patients with higher genetic risk respond differently to treatment or require more targeted lifestyle interventions.

“We want to understand whether people with higher genetic risk need a different type of pre-vention or treatment than others.”

In practice, this entails translating complex genetic data into simple tools that clinicians can use in everyday settings.

“An idea is that the risk assessment tool can provide a simple stoplight signal in the patient health register platform (Sundhedsplatform) during every screening visit – green, yellow or red. For clinicians this might be useful and could lead to better patient treatment and disease prevention,” says Tarunveer S. Ahluwalia.