Characterizing Functional Genetic Variants Linking Immunity and Schizophrenia

• Applicant: Dr. Sarah Kim-Hellmuth
• Subject Area: Human Genetics ; Immunology
• Term: from 2016 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 316802077

Understanding genetic risk for disease is one of the major goals in human genetics. Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with complex human diseases, the majority of them located in regulatory regions outside of genes. The identification of functional regulatory variants underlying such GWAS associations and understanding their pattern of activity is the key for understanding biological processes behind each genetic association to disease. This understanding is essential for the development of targeted interventions and to tailor personalized therapies.Schizophrenia (SCZ) is among the most disabling and economically catastrophic medical disorders, ranked by the World Health Organization as one of the top ten illnesses contributing to the global burden of disease. In the last several years, many genomic regions that influence SCZ risk have been identified. However, the individual genetic variants that cause disease risk, and the biological mechanisms by which they do so, remain unclear. Aim of the project is the functional characterization of the SCZ risk variant rs13107325. Current work by the applicant shows that this SNP is a response expression quantitative trait locus (reQTL) after immunstimulation, thereby linking immunity and SCZ pathology. To study the functional role of this variant the applicant will combine state-of-the-art technologies in genome engineering, next-generation sequencing and computational biology, which will allow obtaining mechanistic insight into genetic risk of human diseases at unprecedented depth. The impact of the project could be enormous, since elucidating the molecular mechanisms of disease-associated variants that link immune function to disease pathology of schizophrenia could contribute to the development of novel treatments for this disease.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Dr. Tuuli Lappalainen