Scientists discover a surprising link between blood type and stroke risk

Stroke doesn’t wait for old age. Adults in their 20s, 30s, 40s, and 50s show up in emergency rooms every day with sudden weakness, trouble speaking, or vision loss. In many stroke cases, a blood clot blocks an artery that feeds the brain. Without fresh, oxygen‑rich blood, brain cells die fast.

Doctors call these events early‑onset ischemic strokes when they happen between ages 18 and 59.

They’re less common than strokes in older adults, but they hit people who may be in school, working, or raising families. Many want to know why it happened and whether genes play a part.

Meta-analysis of stroke victims

A team of scientists led by University of Maryland School of Medicine (UMSOM) did a meta-analysis, searching the human genome for answers.

“The number of people with early strokes is rising,” said study co-principal investigator Steven J. Kittner, MD, MPH, Professor of Neurology at UMSOM.

“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,”

Kittner and his team combined 48 studies and compared about 16,730 adults who had an early‑onset ischemic stroke with nearly 600,000 adults who had not had a stroke.

They used a genome‑wide association study (GWAS), which scans millions of common DNA differences and asks whether any show up more often in people with the disease.

Each small DNA change offers a tiny clue. Most of these common variants don’t act alone. Many nudge risk up or down by a little bit. Add those nudges across very large groups, and patterns start to stand out.

What the genome scan found

One region stood out: the ABO gene, which helps determine blood type A, B, AB, or O. The strongest signals in the scan clustered in this region.

Two specific genetic markers there pushed risk in opposite directions, a pattern that fits known biology of clot formation.

That opposite push matters. It signals that some versions of the ABO region raise the chance a clot will form and travel toward the brain, while others lower it.

Blood type and stroke

The ABO gene does more than set letters on red blood cells. It also helps set levels of clotting‑related proteins, especially von Willebrand factor and factor VIII.

People with non‑O blood types tend to have higher levels of these proteins, and the A1 subgroup usually sits near the high end of that range.

Higher levels of von Willebrand factor and factor VIII can make clots more likely. That connection explains why ABO biology shows up in a study of early stroke, which often begins with a clot.

Shared genetic signals

The team tested whether the same DNA signals in ABO influence several traits at once. They compared the markers tied to early‑onset stroke with markers tied to von Willebrand factor, factor VIII, and venous thromboembolism (VTE), a condition where clots form in veins.

They found strong evidence that the same underlying genetic signals in the ABO region affect all these traits, and statistical tests supported shared causes rather than random overlap.

VTE often appears as a deep‑vein clot in a leg or as a clot that breaks off and travels to the lungs. Doctors already link higher von Willebrand factor and factor VIII levels to a greater chance of venous clots.

The genetic overlap connects these clinical observations to specific differences in ABO.

“Our meta-analysis looked at people’s genetic profiles and found associations between blood type and risk of early-onset stroke,” explained study co-principal investigator Braxton D. Mitchell, PhD, MPH, Professor of Medicine at UMSOM.

“The association of blood type with later-onset stroke was much weaker than what we found with early stroke.”

Real-world blood type and stroke

Genetic markers tell one part of the story; actual blood types tell another. People with early‑onset ischemic stroke were more likely to have blood group A and less likely to have blood group O than comparison groups.

The B subgroup did not show a strong association with early stroke in this study, unlike patterns sometimes seen with venous clots.

These real‑world blood group patterns line up with the DNA signals near ABO. They point to blood‑type biology as a key piece of early stroke risk.

“We still don’t know why blood type A would confer a higher risk, but it likely has 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 Dr. Kittner.

Fine‑grained clues inside ABO

One genetic marker tagged the O1 blood subgroup and was linked to about a 12 percent reduction in the odds of early stroke.

Another marker tagged the A1 subgroup and was tied to about a 16 percent increase. The story is not as simple as “any non‑O type is bad.”

These opposite directions help explain why some people with certain ABO subgroups face higher risk while others see some protection.

Limits and what comes next

Even with its large numbers, the project has limits. It is one of the biggest genetic studies of early‑onset ischemic stroke so far, but it was still smaller than some studies in other diseases, so very small genetic effects may have gone undetected.

Most participants had European ancestry, even though the study included people from other backgrounds.

Because genetic variants can differ in frequency and effect across populations, larger and more diverse studies will sharpen the picture.

Blood type, stroke, and future health

Stroke risk does not arise from DNA alone. Blood pressure, smoking, diabetes, unhealthy cholesterol levels, infections, hormones such as those in some oral contraceptives, and everyday habits involving sleep, diet, and exercise all play roles.

The findings point toward clotting‑related genetics having a stronger influence on strokes that happen earlier in adult life than on strokes that occur at older ages.

Future work can test prevention strategies that mix lifestyle information, medical history, and genetics for people who might benefit most.

“This important and surprising research finding adds to our current knowledge about non-modifiable risk factors for stroke – including a person’s blood type,” said Mark T. Gladwin, MD, Vice President for Medical Affairs at University of Maryland, Baltimore.

“This study also highlights the need for future research to sort out the connection of blood group with clotting risk in more diverse populations. This will help us to better understand the strength of this association across different races and ethnicities.”

The full study was published in the journal Neurology.

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