Chengran C. Yang, United States of America
Washington University in St. Louis PsychiatryPresenter of 2 Presentations
LIVE DISCUSSION
INTEGRATIVE MULTI-TISSUE MULTI-OMICS FOR BIOMARKER AND THERAPEUTIC TARGET DISCOVERY IN ALZHEIMER DISEASE (AD) AND PARKINSON DISEASE (PD)
Abstract
Aims
To identify causal pathway of AD and PD risk and drug targets by generating and analyzing multi-tissue proteomic and genetic data from a large cohort.
Methods
We generated a genomic atlas of protein levels in multiple neurologically relevant tissues (380 brain, 835 cerebrospinal fluid (CSF) and 529 plasma), by profiling thousands of proteins in a large and well-characterized cohort. We used Mendelian Randomization (MR) and colocalization methods to identify proteins in the causal pathway of two neurological diseases and drug targets for repurposing.
Results
Combining both MR and colocalization results, we found that one CSF, 13 plasma and six brain proteins were likely to be in the causal pathways for AD risk. Among these proteins, plasma CD33 was a risk factor towards AD and had been used as a drug target for other diseases, such as prostate cancer. As for PD risk, 13 CSF, 12 plasma and 23 brain proteins were likely to be the cause. Among these proteins, plasma IDUA was prioritized as it was encoded by a risk locus for PD and as a drug target for chondroitin sulfate, reported to treat osteoarthritis. IDUA is required for the lysosomal degradation of glycosaminoglycans, dermatan sulfate and heparan sulfate.
Conclusions
Our results prioritized several proteins likely to be in the causal pathways leading to AD and PD risk. These nominated proteins can facilitate mapping the disease GWAS results into biological mechanisms, and further leading to precision medicine in neurological and/or psychiatric traits.