Neurogenetic Systems Analysis

Our research on complex diseases of the neural system addresses disorders of cognition such as frontotemporal dementia and disorders of movement and of sleep such as restless legs syndrome (RLS). The latter is rather common with a prevalence of up to 10% in elderly Europeans. RLS is characterized by an irresistible urge to move the legs accompanied by disagreeable, painful sensations in the lower limbs at night. As a consequence, patients suffer from severe insomnia resulting in an impairment of quality of life and wellbeing. It is a lifelong disorder with progressive symptoms. By studying the genetics and epigenetics of RLS, we aim for understanding the pathophysiology of the disease and for developing useful disease predictors. We apply statistical modelling and deep learning algorithms in order to integrate genetic, epigenetic and environmental factors.

As opposed to common diseases that usually are polygenic and multifactorial, many rare diseases are monogenic, that is, they are caused by one strong, highly penetrant genetic effect. The features of neurological diseases thus may be very specific for the respective etiologies. We examine genome-wide DNA methylation patterns as such disease-specific features, especially in case of monogenic disorders of the epigenetic machinery such as dystonia with KMT2B-deficiency and Kabuki syndrome due to KMT2D deficiency.