Researchers from the LMU Klinikum Munich are significantly involved in the worldwide analysis of the Gigastroke consortium.
Genomics is the analysis of a person’s entire genome with regard to a specific question. It is an effective method of getting an overview of which sections (loci) of the human genome could be involved in the development and molecular events of a specific disease – for example a stroke. In a gigantic international genomics study, which they combined with other methods, researchers at the LMU Klinikum Munich have now discovered that 89 sections of the human genome are involved in the development of a stroke. The results point to new ways of diagnosing and treating stroke and have now been published online in the scientific journal Nature.
In Germany alone, 260,000 to 280,000 people suffer a stroke every year – this means that such an event occurs every two to three minutes in this country. Stroke is the leading cause of permanent disability and the second leading cause of death worldwide after heart attack. Countless years of life are lost to stroke every year, especially in low- and middle-income countries. “A global perspective of stroke research is therefore essential,” says Prof. Dr. Martin Dichgans from the Institute for Stroke and Dementia Research at the LMU Klinikum in Munich.
Knowing this, the experts of the worldwide so-called GIGASTROKE consortium examined the blood samples of more than two and a half million people, almost 200,000 of whom had suffered a stroke. The genetic material DNA with the 20,000 genes encoded in it was isolated from all blood samples and analyzed using high-tech methods of modern genomics and bioinformatics. The participants came from Europe, East Asia, Africa, South Asia and Latin America. “This diversity offers the opportunity to gain new genetic connections and a more in-depth understanding of the biological connections in stroke,” says Prof. Dr. Stephanie Debette from the Bordeaux University Hospital. The doctor and her Munich colleague Prof. Dr. Dichgans lead the GIGASTROKE Consortium. Tokyo University (Japan), Tartu University (Estonia), Ibadan University (Nigeria), VA Boston Healthcare System and Harvard Medical School (USA) are also significantly involved.
New findings also for prevention and therapy
First, the researchers analyzed the genomes of 1.6 million people (110,000 with a stroke). In the course of this, 89 sections of the genome were discovered that are involved in a stroke and that largely overlap worldwide. Of these sections, 61 had not previously been associated with stroke. Each of these 89 places in the genome contains different genes. The scientists then analyzed the suspicious regions again in the DNA samples of another 1.1 million people (89,000 with stroke) to confirm their results.
The researchers then combined the genomic data with other methods of gene and protein research in order to explore specific starting points (individual genes or proteins) for new drugs. For two of these starting points, new active ingredients are already being tested in the first clinical studies, which are intended to prevent strokes in patients at risk. The researchers also found indications that existing drugs for other diseases could also help in the prevention and treatment of strokes. “That,” says Dichgans, “proves the clinical value of our approach.”
Better prediction of individual risk of stroke
From all the risk factors found for a stroke, the scientists finally developed a so-called polygenic score. This score, it turned out, reflects very well the individual stroke risk for people from Europe and East Asia. The available data were not yet sufficient for a score for the African population.
Last but not least, the team led by Martin Dichgans and Stephanie Debette evaluated data from 52,600 patients from five clinical studies – and showed that the new genetic risk factors predict the likelihood of a stroke much better than the traditional clinical risk factors (high blood pressure, smoking and so on further).
“It is not yet clear when these findings will find their way into everyday clinical practice,” emphasizes Prof. Dichgans, “but the basis for this has definitely been laid with this study.”