Stroke Identified previously unknown risk factors

In a mega-study, the genetic data of about 500,000 subjects were examined to find the causes of a stroke in the genome.

• stroke
• vascular disease
• causes
• heritage
• Mega study

Indications of previously unknown mechanisms that trigger a stroke

Although stroke is the number two cause of death worldwide, the molecular mechanisms and potential genetic causes of vascular disease have not been fully explored. In a megacontact, scientists have now gained new insights into the development of stroke.

In a meta-analysis, researchers have examined the genetic data of over half a million study participants to find the causes of a stroke in the genome. (Image: psdesign1 / fotolia.com)

Reduce cerebral infarction risk

In Germany, around 270,000 people suffer a stroke each year. The so-called cerebral infarction is one of the most common causes of death in this country.

It is well known that one can reduce the risk of stroke through a healthy lifestyle with healthy diet, physical activity, avoiding obesity and normal cholesterol levels and preventing certain risk factors such as high blood pressure, type 2 diabetes, atrial fibrillation and lipid metabolism disorders but the molecular mechanisms and possible genetic causes of cerebral infarction have not yet been sufficiently researched.

In a genome-wide association study, the international research consortium "Megastroke" has now examined the genome of more than 520,000 test persons for possible genetic risk factors.

The analysis shows a total of 32 loci that are associated with stroke - about three times as many as previously known, reports the Ludwig Maximilian University (LMU) Munich in a statement.

Genetic predisposition to stroke

"Megastroke" is the world's largest study of its kind to date for the genetic predisposition to stroke.

Research groups led by Martin Dichgans, Professor of Neurology, Director of the Institute for Stroke and Dementia Research (ISD) at the LMU, and researchers at the German Center for Neurodegenerative Diseases (DZNE) and epidemiology professor Stephanie Debette from the University of Bordeaux coordinated the study , in which around 180 institutions participated.

The meta-analysis evaluated data from nearly 30 large studies. Of the more than half a million subjects whose data were included in the study, there were approximately 67,000 stroke patients.

The results have recently been published in the journal "Nature Genetics".

Changes in different parts of the vascular system

Strokes can be triggered by changes in various parts of the vascular system: in the large arteries and the small vessels, the heart and the venous vessels.

"From the study, we learned a lot about the genetic architecture that underlies the onset of stroke," said Martin Dichgans.

The researchers found that many of the 32 gene loci are in part coincident with genitalia associated with other diseases such as hypertension, hyperlipidemia, atrial fibrillation, coronary artery disease, and venous thrombosis.

So gene variants that lead to high blood pressure, for example, come as a trigger of stroke in question.

As the data come from studies from around the world, scientists can also show that the weighting of risk factors differs slightly in different ethnic groups.

Reference to new, previously unknown mechanisms

"It is surprising that for half of the 22 newly found gene loci no overlap to previously known risk factors can be found," said Dichgans.

This suggests new, previously unknown mechanisms that trigger a stroke - and possibly targets of new therapies. The researchers also found common genetic risk factors for the two major forms of stroke.

They found overlaps of loci contributing to the risk of stroke due to vascular occlusion and those associated with the rupture of a blood vessel.

This suggests common mechanisms of development, independent of known risk factors, such as hypertension.

First step to a personalized treatment

By completing the investigations with data on the expression of genes and proteins and other characteristics of a wide variety of cell types and tissues collected by scientists from the participating institutions, researchers were able to gain insight into which genes, molecular mechanisms, and cell types are the genetic risk of stroke now make up found gene loci.

Part of the 32 gene loci showed overlaps with areas whose gene products are targets of two common antithrombotic therapeutics: a plasminogen activator involved in clot breakdown and an agent that inhibits clumping of platelets into clots.

"These findings demonstrate the importance of genetic studies for drug development," said Dr. Rainer Malik from the ISD, one of the first authors of the study.

In fact, according to the expert, the results of the study could be seen as "a first step towards a personalized, evidence-based treatment of this highly complex disease". (Ad)