This project will undertake pre-clinical and cohort studies that address susceptibility factors for paediatric and adolescent tic disorders, with a particular focus on comorbid obsessive-compulsive symptomatology, from clinical, epidemiological, genetic, microbiological and immunological angles. EMTICS aims to elucidate the complex aetiology of the onset and clinical course of chronic tic disorders and associated obsessive-compulsive symptoms, through disentangling the interplay between environmental factors and genetic background; translate research findings into clinical applications by developing disease prediction models and investigation of a treatment strategy; and will establish a Pan-European infrastructure for the study of tic disorders. We hypothesise that the onset and/or exacerbation of tic and comorbid obsessive-compulsive disorders is associated with increased preceding occurrence of Group A beta-haemolytic Streptococcus (GAS) infections of specific molecular subtypes, and that this association is based on genetic susceptibility factors and mediated through immunological mechanisms related to psychosocial stress and immunological factors in host and GAS strains. Large-scale cohort studies will involve affected patients and at-risk first-degree relatives within an integrated, multidisciplinary research strategy. Treatment effects of active surveillance and standardized antibiotic treatment of GAS colonisation, thus addressing one of the main environmental factors involved (GAS infections) will be evaluated. Our approach will result in the identification of genetic and environmental susceptibility factors and will greatly contribute to a better understanding of the underlying mechanisms of tic disorders, with a focus on elucidating the role of autoimmunity. Our consortium brings together the highest expertise in the field of tic disorders across Europe in academia and industry, including a number of SMEs and a professional management company.