Mapping the serum proteome to neurological diseases using whole genome sequencing.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34857772.
- Also identified by DOI 10.1038/s41467-021-27387-1 and PMC identifier 8640022.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Despite the increasing global burden of neurological disorders, there is a lack of effective diagnostic and therapeutic biomarkers. Proteins are often dysregulated in disease and have a strong genetic component. Here, we carry out a protein quantitative trait locus analysis of 184 neurologically-relevant proteins, using whole genome sequencing data from two isolated population-based cohorts (N = 2893). In doing so, we elucidate the genetic landscape of the circulating proteome and its connection to neurological disorders. We detect 214 independently-associated variants for 107 proteins, the majority of which (76%) are cis-acting, including 114 variants that have not been previously identified. Using two-sample Mendelian randomisation, we identify causal associations between serum CD33 and Alzheimer's disease, GPNMB and Parkinson's disease, and MSR1 and schizophrenia, describing their clinical potential and highlighting drug repurposing opportunities.
Medical subject headings
- Alzheimer Disease
- Membrane Glycoproteins
- Parkinson Disease
- Scavenger Receptors, Class A
- Schizophrenia
- Sialic Acid Binding Ig-like Lectin 3