Spatially resolved mapping of cells associated with human complex traits

This is an online event held via Zoom: https://uni-sydney.zoom.us/j/85114748391

Depicting spatial distributions of disease-relevant cells is crucial for understanding disease pathology. In our recent work, we developed a method, gsMap, that integrates spatial transcriptomics (ST) data with genome-wide association study (GWAS) summary statistics to map cells to human complex traits, including diseases, in a spatially resolved manner. Using embryonic ST datasets covering 25 organs, we benchmarked gsMap through simulation and by corroborating known trait-associated cells or regions in various organs. Applying gsMap to brain ST data, we revealed that the spatial distribution of glutamatergic neurons (glu-neurons) associated with schizophrenia more closely resembles that for cognitive traits than that for mood traits, such as depression. The schizophrenia-associated glu-neurons were distributed near the dorsal hippocampus, with upregulated calcium signaling and regulation genes, while the depression-associated glu-neurons were distributed near the deep medial prefrontal cortex, with upregulated neuroplasticity and psychiatric drug target genes.