Gene variants associated with blood type may contribute to risk of early stroke

Gene variants associated with a person's blood type may be linked to their risk of early stroke, according to a new meta-analysis published in the August 31, 2022, online issue of Neurology^®, the medical journal of the American Academy of Neurology. The meta-analysis included all available data from genetic studies that included young adult ischemic stroke, which is caused by a blockage of blood flow to the brain.

Non-O blood types have previously been linked to a risk of early stroke, but the findings of our meta-analysis showed a stronger link between these blood types with early stroke compared to late stroke, and in linking risk mostly to blood type A. Specifically, our meta-analysis suggests that gene variants tied to blood types A and O represent nearly all of those genetically linked with early stroke. People with these gene variants may be more likely to develop blood clots, which can lead to stroke."

Braxton D. Mitchell, PhD, MPH, Study Author, University of Maryland School of Medicine in Baltimore

The meta-analysis involved a review of 48 studies on genetics and ischemic stroke from North America, Europe and Asia. The studies included 16,927 people with stroke and 576,353 people who did not have a stroke. Of those with stroke, 5,825 people had early onset stroke and 9,269 people had late onset stroke. Early onset stroke was defined as an ischemic stroke occurring before age 60 and late onset stroke was older than 60.

Researchers looked across all the chromosomes to identify genetic variants associated with stroke. They found a link between early stroke and the area of the chromosome that includes the gene that determines A, AB, B or O blood type.

They then divided participants into A, AB, B and O blood types. They compared the prevalence of those blood types in people with early stroke, late stroke and people who did not have a stroke.

Researchers found that people with early stroke were more likely to have blood type A and less likely to have blood type O compared to people with late stroke and people without stroke. Both early and late stroke were also more likely to have blood type B compared to controls.

When looking at people of European ancestry and comparing 5,825 people with early stroke to 29,320 people who did not have a stroke, the meta-analysis found that 48% of people with early stroke had blood type A compared to 45% of people with late stroke and 44% of people without stroke. They also found 35% of people with early stroke had blood type O compared to 39% of those with late stroke and 41% of people without stroke.

After adjusting for sex and other factors, researchers found those who had blood type A had an 18% higher risk of having an early stroke than people with other blood types. Those who had blood type O had a 12% lower risk of having a stroke than people with other blood types.

"This work deepens our understanding of early onset stroke development and changes," said Jennifer Juhl Majersik, MD, MS, of the University of Utah and Fellow of the American Academy of Neurology, who wrote an editorial accompanying the study. "Future research is needed to help develop a more precise understanding of how stroke develops. This could lead to targeted preventative treatments for early onset stroke, which could result in less disability during people's most productive years."

A limitation of the study was the limited amount of diversity among participants, although 35% of the participants were of non-European ancestry.

The study was supported by the National Institutes of Health and Department of Veterans Affairs.