Cambridge MA, USA, Kiel, June 22, 2018. In the most comprehensive international collaboration to date on the molecular-genetic basis of diseases of the central nervous system, the international research consortium with the participation of scientists from the Kiel Pain Clinic discovered genetic connections between psychiatric and neurological diseases. The research group was made up of more than 600 institutions worldwide. The discoveries far overshadow previous knowledge on the subject. The team discovered that psychiatric disorders share extensive genetic similarities. In contrast, neurological diseases are genetically clearly separated. In a study published today in the scientific journal Science, the authors describe the results of the most comprehensive data set to date on the genetic connections between brain diseases. The findings show that mental illnesses share significant similarities at the molecular level that are not reflected by today's current diagnostic categories. The findings indicate that there needs to be a new way of thinking about the development, diagnosis and treatment of diseases of the central nervous system.

If the genetic connections and the pattern of overlap in the molecular-genetic basis of various diseases can be uncovered, the conditions that cause these diseases can also be better understood. As a result, specific mechanisms can then be identified that offer targets for tailored treatments.

For the current study, international research consortia pooled their data to analyze the genetic patterns of 25 psychiatric and neurological diseases. The findings were only made possible by compiling all data worldwide in the largest international analysis on this topic to date. The research group recorded genetic overlap using genome-wide association studies (GWAS) from 265,218 patients and 784,643 controls. The research project used data from several hundred researchers to deepen our understanding of how the brain works. This is a first-of-its-kind event.

The main finding was that there is a large overlap in the molecular basis of psychiatric diseases. This particularly applies to attention deficit hyperactivity syndrome (ADHD), manic-depressive illnesses, depressive episodes and schizophrenia. The data also demonstrate a strong overlap in the molecular basis of anorexia nervosa, obsessive-compulsive disorder and Tourette syndrome.

In contrast, the molecular basis of neurological diseases such as: B. Parkinson's disease or multiple sclerosis are more clearly independent. However, an exception was migraine with aura and migraine without aura. This widespread headache disorder, which is one of the most debilitating diseases in humans according to the World Health Organization (WHO), has shown genetic connections between attention deficit hyperactivity disorder, depressive disorders and Tourette syndrome.

This is the most comprehensive study to date on the genetic connections between diseases of the central nervous system and demonstrates the tangible genetic basis of psychiatric and neurological diseases. Prof. Dr. Hartmut Göbel, co-author and chief physician at the Kiel Pain Clinic, comments on the results: “The complexity of migraine as a special neurological disease is reflected in significant connections with both psychological and neurological symptoms. Migraine is therefore rightly called the encyclopedia of neurology. The data also demonstrate the comprehensive symptoms of migraines. They also make it understandable why the risk of mental illnesses such as depression, anxiety and personality changes is increased by a factor of 8 in migraine patients. They also highlight the common underpinnings of cerebrovascular disease and migraine with the increased risk of stroke and cardiovascular disease.”

A key conclusion is that today's diagnostic categorization of brain disorders does not accurately reflect the underlying biological reality. The diagnostic classification of these disorders may not adequately reflect the mechanisms by which these disorders arise within the central nervous system and cause overlapping symptoms.

Further breakdown of these genetic connections can lead to new clinical syndromes being differentiated and the development of new treatment methods and the selection of patients for effective treatments can be carried out more precisely. A limited association was found for comorbidity between migraine with aura and ischemic stroke. The subtypes of migraine, migraine without aura and migraine with aura, also showed substantial genetic connections. For neurological diseases, it was clear that Alzheimer's disease, intracerebral hemorrhage, ischemic stroke and migraine had significant negative genetic associations with cognitive variables.

 

Source: Science 22 Jun 2018:Vol. 360, Issue 6395, eaap8757, DOI: 10.1126/science.aap8757

Analysis of shared heritability in common disorders of the brain: By The Brainstorm Consortium
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