In a mega-study, the genetic data of around 500,000 subjects were examined to find the causes of a stroke in the genome.
- Vascular disease
- 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 possible genetic causes of vascular disease have not yet been sufficiently researched. In a mega study, scientists have now gained new insights into the development of stroke.
Reduce risk of heart attack
Around 270,000 people suffer a stroke in Germany every year. The so-called brain infarction is one of the most common causes of death in Germany.
It is known that you can reduce the risk of stroke by a healthy lifestyle with a healthy diet, physical activity, avoiding obesity and normal cholesterol levels and by preventing certain risk factors such as high blood pressure, type 2 diabetes, atrial fibrillation and fat metabolism disorders , but the molecular mechanisms and possible genetic causes of brain infarction have not been adequately researched.
The international research consortium "Megastroke" has now examined the genome of more than 520,000 subjects for possible genetic risk factors in a genome-wide association study.
The analysis shows a total of 32 gene locations that are associated with stroke - around three times as many as previously known, reports the Ludwig Maximilians University (LMU) Munich in a message.
Genetic predisposition to stroke
“Megastroke” is the largest study of its kind in the world to date regarding 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 the epidemiology professor Stephanie Debette from the University of Bordeaux coordinated the study , in which around 180 institutions participated.
As part of the meta-analysis, data from almost 30 large studies were evaluated. Around 67,000 of the more than half a million subjects whose data were used in the study were stroke patients.
The results were recently published in the journal "Nature Genetics".
Changes in different parts of the vascular system
Strokes can be triggered by changes in different parts of the vascular system: in the large arteries and small vessels, the heart and the venous vessels.
"We learned a lot from the study about the genetic architecture underlying the development of the stroke," said Martin Dichgans.
The researchers found that many of the 32 gene locations partially correspond to genome sections that are associated with other diseases such as hypertension, hyperlipidemia, atrial fibrillation, coronary artery disease and venous thrombosis.
Gene variants that lead to high blood pressure, for example, can also be used to trigger a stroke.
Since the data comes from studies from all over the world, the scientists can also show that the weighting of the 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 locations there is no overlap with previously known risk factors," says Dichgans.
This indicates new, previously unknown mechanisms that trigger a stroke - and possibly the target of new therapies. The researchers also found common genetic risk factors for the two main forms of stroke.
They found overlaps between the gene locations that contribute to the risk of stroke due to vascular occlusion and those associated with the rupture of a blood vessel.
This indicates common development mechanisms, regardless of known risk factors, such as high blood pressure.
First step to personalized treatment
By supplementing the investigations with data on the expression of genes and proteins and other characteristics of various cell types and tissues, which scientists from the institutions involved had brought together, the researchers were able to gain first insights into which genes, molecular mechanisms and cell types are the genetic risk of stroke now identify the loci found.
Some of the 32 gene locations showed overlaps with areas whose gene products are targets for two common antithrombotic therapeutics: a plasminogen activator, which is involved in the breakdown of blood clots, and an active ingredient that inhibits the aggregation of the platelets into clots.
"These findings demonstrate the importance of genetic studies for drug development," said Dr. Rainer Malik from ISD, one of the first authors of the study.
In general, according to the expert, the results of the study can be seen "as a first step towards personalized, evidence-based treatment of this highly complex disease". (ad)