Mapping the serum proteome to neurological diseases using whole genome sequencing.
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Authors
Barysenka, Andrei
Repetto, Linda
Tsafantakis, Emmanouil
Karaleftheri, Maria
Dedoussis, George
Gilly, Arthur
Publication Date
2021-12-02Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
12
Issue
1
Number
7042
Pages
7042
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Png, G., Barysenka, A., Repetto, L., Navarro, P., Shen, X., Pietzner, M., Wheeler, E., et al. (2021). Mapping the serum proteome to neurological diseases using whole genome sequencing.. Nat Commun, 12 (1. 7042), 7042. https://doi.org/10.1038/s41467-021-27387-1
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.
Sponsorship
Medical Research Council (MC_UU_12015/1)
MRC (MC_PC_13046)
Identifiers
External DOI: https://doi.org/10.1038/s41467-021-27387-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/331372
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