Control of gene expression in human neuronal development and neuropsychiatric diseases

The overall aim is to understand brain development, especially in the context of neuropsychiatric disorders.

We work now toward four Specific Aims: 1) We have identified 47351 active transcriptional enhancers (TEs), out of which 31057 (66%) new, and found their enrichment among genome-wide association study SNPs for neuropsychiatric diseases, notably schizophrenia, Parkinson’s disease and dyslexia.2) We identify cognate motifs for transcription factor binding at these sites.3) We construct a regulatory network of neuronal differentiation based on the transcription factor binding sites and protein-protein interaction study.4) We aim to provide models for disease mechanisms and validate the findings by directed functional experiments.The applicant’s laboratory led enhancer identification and has published earlier using all the methods needed in this project.

We involve international collaborations for expertise in specialized large-scale analyses.The identification of TEs, cognate transcription factors, and protein networks increase understanding of neuronal differentiation and function.

We combine data from genome-wide association studies (GWAS) on neuropsychiatric diseases.This project is primarily basic research with high translational value to provide detailed information on the GWAS associations in neuropsychiatric disorders.

The expected findings will provide mechanistic understanding of GWAS associations and may provide starting points for pharmaceutical development.