Genome sequencing has transformed our ability to find genetic variants linked to disease. Most disease-associated variants fall in regulatory DNA, where their effects are far hard to interpret, and we often cannot say which gene a variant affects, in which cell type, or at what point in development.

This is an important gap. More than 50% of children with a neurodevelopmental disorder still have no genetic diagnosis after whole-genome sequencing, leaving families without an explanation. In Alzheimer's disease, inherited risk is concentrated in regulatory elements active in microglia, the brain's immune cells, yet how these variants alter microglial function is largely unknown.

By mapping regulatory elements to the genes they control, and testing them directly in human brain cells, we aim to make non-coding variation interpretable -  adding mechanistic understanding to associations, in order to provide candidate targets for treatment.