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U of A study examines how environmental and genetic factors impact stroke risk

Identifying factors that contribute to stroke risk would aid stroke prediction and ultimately prevention, Jickling said.

A University of Alberta research team will receive $4.79 million in funding over four years to study risk factors involved in stroke development. The study will examine blood samples from 3,200 stroke patients to establish a blood-based biomarker for the risk of experiencing a stroke.

Glen Jickling, a co-lead on the study, is a neurologist and Canada Research Chair in Genomics and Genetics of Stroke. Jickling is also an associate professor in the neurology division of the U of A’s department of medicine.

“Stroke is an injury to the brain. There are two types of stroke. One is a blockage of blood flow to the brain … and the other is a bleeding in the brain,” Jickling said. 

Stroke is the third leading cause of death in Canada. National data from 2017–2018 shows about 878,500 Canadian adults over the age of 20 have experienced a stroke. Some risk factors for stroke include obesity, diabetes, and high blood pressure, which is a major risk factor.

Jickling also cited age as one of the risk factors for experiencing a stroke.

David Wishart, a co-lead on this study, is a distinguished university professor at the U of A’s department of biological sciences. He serves as Canada Research Chair in Metabolomics and Precision Medicine. Wishart’s bioinformatics courses focus on the use of computational tools for analyzing molecular biology data.

The project will obtain blood samples from 3,200 Canadian stroke patients and store them in a biobank. The U of A currently houses a biobank for stroke patients across Canada.

“The biobank [at the U of A] has a couple thousand patients who have had a stroke … and this project will enable it to expand beyond U of A into hospitals across Canada,” Jickling said.

Genetics and environment

Patients’ blood samples will undergo whole genome sequencing to determine the genetic makeup of each participant. This will help identify stroke-related genetic variants across participants.

According to Jickling, the goal of the study is to “understand how those genetic variants are different in people who have a stroke versus those who don’t have a stroke.”

In addition to looking at genes themselves, gene products such as transcriptomics (transcripts) and proteomics (proteins) will also be measured. Measurements will be done “in the thousands of molecules,” Jickling said. 

The presence of certain genetic variants alone does not precisely predict someone’s risk of having a stroke, according to Jickling.

It’s often an interaction of yes, you have the gene, plus you’re exposed to a certain environmental stimulus, and those team up together to produce a disease,” Jickling said. “Finding those patterns or interactions needs a larger sample size, that’s why it’s in the order of thousands of patients.” 

The study aims to generate polygenic risk scores to indicate individuals’ risk of experiencing a stroke. Jickling explained that the presence of more stroke-related genetic variants would put someone at a higher risk for stroke. Jickling believes this score, combined with measured environmental factors, would improve individual stroke risk prediction.

Another goal of this study is to “understand what’s driving stroke” to “implement better stroke prevention therapy,” Jickling said.

Limitations of current treatment

The current limitations of stroke treatment highlights the need for stroke prevention. For strokes caused by a blood clot in the brain, patients take clot-buster drugs to break the clot and open up the blood vessel.

The main limitation with clot-busting drugs, according to Jickling, is that they “have to be given within four and a half hours of stroke onset.”

“And when given, it only works in about 30 per cent of patients.”

For patients with a large blood clot in a large artery, a catheter is guided to the brain to remove the clot — these patients make up “less than five per cent of stroke patients,” Jickling said. 

The researchers aim to uncover risk factors that contribute to stroke to prevent it altogether.

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