A person’s blood type might be linked to their risk of an early stroke, according to a meta-analysis that included all available data from genetic studies focusing on ischaemic strokes – caused by a blockage of blood flow to the brain, in adults under 60.
The study was led by researchers from the University of Maryland School of Medicine (UMSOM).
“The number of people with early strokes is rising,” said study co-principal investigator Dr Steven Kittner, professor of neurology at UMSOM and a neurologist with the University of Maryland Medical Centre.
“These people are more likely to die from the life-threatening event, and survivors potentially face decades with disability. Despite this, there is little research on the causes of early strokes,” he added.
He and his colleagues performed a meta-analysis of 48 studies on genetics and ischaemic stroke that included 17 000 stroke patients and nearly 600 000 healthy controls who had never had a stroke. They then looked across all collected chromosomes to identify genetic variants associated with a stroke and found a link between early-onset stroke – occurring before 60 – and the area of the chromosome that includes the gene determining whether a blood type is A, AB, B, or O.
The study found that people with early stroke were more likely to have blood type A and less likely to have blood type O (the most common blood type), compared to people with late stroke and people who had never had a stroke. Both early and late stroke were also more likely to have blood type B compared with controls.
After adjusting for sex and other factors, researchers found those with blood type A had a 16% higher risk of an early stroke than people with other blood types. Those with blood type O had a 12% lower risk of having a stroke than people with other blood types.
“Our meta-analysis looked at people’s genetic profiles and found associations between blood type and risk of early-onset stroke. The association of blood type with later-onset stroke was much weaker than what we found with early stroke,” said study co-principal investigator Braxton Mitchell, professor of Medicine at UMSOM.
The researchers emphasised that the increased risk was very modest and that those with type A blood should not worry about having an early-onset stroke or engage in extra screening or medical testing based on this finding.
“We still don’t know why blood type A would confer a higher risk, but it may have something to do with blood-clotting factors, like platelets and cells that line the blood vessels, as well as other circulating proteins, all of which play a role in the development of blood clots,” said Kittner.
Previous studies suggest that those with an A blood type have a slightly higher risk of developing blood clots in the legs (deep vein thrombosis”. “We clearly need more follow-up studies to clarify the mechanisms of increased stroke risk,” he added.
A limitation of the study was the relative lack of diversity among participants. The data was derived from the Early Onset Stroke Consortium, a collaboration of 48 different studies across North America, Europe, Japan, Pakistan and Australia. About 35% of the participants were of non-European ancestry.
“This study raises an important question that requires a deeper investigation into how our genetically predetermined blood type may play a role in early stroke risk,” said Dr Mark Gladwin, executive vice-president for Medical Affairs, UM Baltimore, and the John Z and Akiko K Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. “It points to the urgent need to find new ways to prevent these potentially devastating events in younger adults.”
Study details
Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke.
Thomas Jaworek, Huichun Xu, Brady J Gaynor, John W. Cole, Kristiina Rannikmae, Tara M Stanne, Liisa Tomppo, Vida Abedi, Philippe Amouyel, Nicole D Armstrong, John Attia, Steven Bell, Oscar R Benavente, Giorgio B Boncoraglio, Adam Butterworth, et al.
Published in Neurology on 31 August 2022
Abstract
Background and Objectives
Current genome-wide association studies of ischaemic stroke have focused primarily on late onset disease. As a complement to these studies, we sought to identifythe contribution of common genetic variants to risk of early onset ischemic stroke.
Methods
We performed a meta-analysis of genome-wide association studies of early onset stroke (EOS), ages 18-59, using individual level data or summary statistics in 16,730 cases and 599,237 non-stroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late onset stroke (LOS) and compared polygenic risk scores for venous thromboembolism between EOS and LOS.
Results
We observed genome-wide significant associations of EOS with two variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared to LOS. The odds ratio (OR) for rs529565, tagging O1, 0.88 (95% CI: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared to LOS (p=0.008).
Discussion
The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
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