Human CSF proteogenomics links genetic variation to neurodegenerative disease proteins - PubMed
5 hours ago
- #GWAS
- #neurodegenerative diseases
- #proteogenomics
- Largest single-site CSF genome-wide association study (GWAS) analyzed 7,092 SomaScan proteins in 1,259 individuals.
- Identified 1,971 genome-wide significant pQTLs (954 cis, 971 trans), with 1,409 replicating in an independent CSF dataset.
- Discovered 264 new loci, replicated 511 associations, refined 80 known loci, and identified 265 proxy-based associations.
- Robust discovery concentrated in reliable measurements, highlighting the need for rigorous quality control.
- Enrichment analyses revealed immune/complement and extracellular matrix biology.
- Mendelian randomization prioritized causal proteins for neurodegenerative diseases like Alzheimer's, Parkinson's, Creutzfeldt Jacobs disease, and ALS.