Scientists discover genetic variant tied to increased stroke risk

Apr 15, 2009

Millions of people have a genetic variant linked to increased risk of ischemic stroke, reports an international research team including scientists at The University of Texas Health Science Center at Houston in a study published online by The New England Journal of Medicine on April 15.

Ischemic accounts for nearly 90 percent of all strokes and is caused by blockage of blood to the brain. More than 150,000 Americans succumb to stroke every year, making it the third leading cause of death. Survivors often experience permanent stoke-related disabilities.

Data gleaned from four large genome-wide association studies in the United States and Europe revealed that about 20 percent of whites and 10 percent of blacks have at least one copy of this genetic variant and that each copy increases the risk of by approximately 30 percent.

The contributors from the UT Health Science Center at Houston are on the faculty of the university's Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), which includes the Senator Lloyd and B.A. Bentsen Center for Stroke Research, and The University of Texas School of Public Health.

The team's discovery could lead to the development of new strategies to detect those at increased risk of stroke prior to the onset of symptoms and to the creation of treatments intended to target the molecular mechanisms underlying stroke risk. "This is the first study to identify a common genetic variant influencing the risk of stroke in the United States," said Eric Boerwinkle, Ph.D., one of the study's authors and Kozmetsky Family Chair in at the UT Health Science Center.

The variant was found during an analysis of the genomes, or DNA, of almost 20,000 individuals from the United States and Europe, and, importantly, the study included both whites and blacks. The variant was not associated with increased risk for non-ischemic stroke.

While there have been previous genetic studies on stroke, the researchers wrote in their paper that the "genes underlying the risk of stroke in the general population remain undetermined."

"This research gives us a pointer or a beacon on the genome where we can look further," said Myriam Fornage, Ph.D., one of the study's lead authors and holder of the Laurence & Johanna Favrot Distinguished Professorship in Cardiology at the UT Health Science Center.

The variant was found on chromosome 12 near one gene associated with brain injury repair called NINJ2 and another connected to blood pressure control called WNK1. "Additional research is required because we don't know if NINJ2 is really the culprit," Fornage said.

In the study, researchers combined the results of genome-wide association data gathered from population-based studies comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium.

"These studies, carried out at our Institute of Molecular Medicine and the School of Public Health, illustrate important advances in the detection and prevention of human diseases that can come from the application of the most sophisticated new genetic technologies to the study of devastating diseases such as stroke," said Peter Davies, M.D., Ph.D., executive vice president for research at the UT Health Science Center.

"The discoveries made by the IMM team, and many similar discoveries that are emerging from studies being conducted by other research groups around the world, are providing the foundation for our ability to deliver on the promise of the next era of medicine: the promise to deliver truly personalized health care to our communities and our patients," Davies said.

The human genome is comprised of about 3 billion DNA base pairs. Among individuals, at some of the positions, there are differences in the DNA sequence, which are called single nucleotide polymorphisms (SNPs). The researchers use these SNPs as guideposts to map the locations of disease genes in the genome.

In the study, scientists linked two markers to increased ischemic stroke risk by comparing the genomes of 1,544 individuals who developed stroke with the genomes of 18,058 individuals who did not develop stroke. The novel discoveries were subsequently replicated in separate studies of blacks and whites.

"Identification of genes that predispose to stroke may aid in the identification of persons at increased risk of stroke in whom particularly vigorous attention to preventive measures can be applied," said Philip A. Wolf, M.D., one of the study's lead authors and principal investigator for the Framingham Heart Study in Framingham, Mass., which is in the CHARGE Consortium "It may also lead to the development of medications to reduce this increased stroke risk."

Environmental factors such as cigarette smoking and high blood pressure also influence predisposition to stroke. "Your risk of disease is the combination of your genetic makeup and environmental factors," Boerwinkle said.

"Even though this variant is common, it has a modest effect on stroke risk," Boerwinkle said. "Therefore, everyone, whether they carry this variant or not, should be aware of the risk factors for stroke, such as high blood pressure and smoking, and do everything they can to avoid those risk factors."

Boerwinkle, who is the principal investigator for the largest study in the CHARGE Consortium, The Atherosclerosis Risk in Communities (ARIC) study, said, "We formed a consortium of the largest studies to permit rapid replication. If you only have one study, there is a chance of a false positive. Here we're doing millions of statistical tests and replication is necessary to rule out false positives." ARIC is a prospective epidemiologic study conducted in four U.S. communities and sponsored by the National Heart, Lung and Blood Institute (NHLBI).

Source: University of Texas Health Science Center at Houston (news : web)

Explore further: Down's chromosome cause genome-wide disruption

add to favorites email to friend print save as pdf

Related Stories

Biomarkers improve ischemic stroke prediction

Dec 18, 2008

Testing patient's blood for two proteins or biomarkers that occur when inflammation is present could help doctors identify which patients are more likely to have a stroke, said researchers at Baylor College of Medicine in ...

Cholesterol-lowering drugs and the risk of hemorrhagic stroke

Dec 12, 2007

People taking cholesterol-lowering drugs such as atorvastatin after a stroke may be at an increased risk of hemorrhagic stroke, or bleeding in the brain, a risk not found in patients taking statins who have never had a stroke. ...

High triglycerides, other cholesterol raise risk of stroke

Dec 27, 2007

People with high triglycerides and another type of cholesterol tested but not usually evaluated as part of a person’s risk assessment have an increased risk of a certain type of stroke, according to research published in ...

Recommended for you

Down's chromosome cause genome-wide disruption

6 hours ago

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

Research uncovers DNA looping damage tied to HPV cancer

13 hours ago

It's long been known that certain strains of human papillomavirus (HPV) cause cancer. Now, researchers at The Ohio State University have determined a new way that HPV might spark cancer development – by ...

New therapy against rare gene defects

Apr 15, 2014

On 15th April is the 1st International Pompe Disease Day, a campaign to raise awareness of this rare but severe gene defect. Pompe Disease is only one of more than 40 metabolic disorders that mainly affect children under ...

User comments : 0

More news stories

Down's chromosome cause genome-wide disruption

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

Simplicity is key to co-operative robots

A way of making hundreds—or even thousands—of tiny robots cluster to carry out tasks without using any memory or processing power has been developed by engineers at the University of Sheffield, UK.

Progress in the fight against quantum dissipation

(Phys.org) —Scientists at Yale have confirmed a 50-year-old, previously untested theoretical prediction in physics and improved the energy storage time of a quantum switch by several orders of magnitude. ...