Integrative gene expression studies on the path to precision medicine in Alzheimer’s and related disorders
Nilufer Ertekin‐Taner- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Genetic studies in Alzheimer’s disease and related disorders (ADRD) revealed numerous disease risk loci many of which reside in noncoding regions. To translate these discoveries to precision medicine therapies and biomarkers, integrative multi‐omics studies especially combining gene expression and disease phenotypes are necessary.
Method
In this presentation, we will review existing and emerging approaches in the discovery of functional disease risk variants, pathways and key disease molecules in ADRD via integrating multi‐omics and disease phenotypic data using computational systems biology followed by experimental validation.
Results
Integrative genome‐wide association studies (GWAS) of ADRD risk, ADRD‐related phenotypes, gene expression and epigenetic factors such as methylation nominate disease variants and pinpoint risk mechanisms. Large scale differential gene and co‐expression network analyses discovered novel disease pathways unique to or shared between different ADRD. Experimental validations of these findings in model systems yielded high confidence molecular perturbations in ADRD.
Conclusion
ADRD is characterized by molecular perturbations in myriad pathways including vascular, synaptic, immune, myelination and many others that are revealed through integrative multi‐omics studies in well‐characterized human cohorts and prioritized through experimental model systems. These molecules serve as candidate precision medicine therapeutic targets and biomarkers.