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Mapping the serum proteome to neurological diseases using whole genome sequencing.
Nat. Commun. 12:7042 (2021)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Large-scale Metaanalysis; Obstructive Sleep-apnea; Alzheimers-disease; Wide Association; Schizophrenia; Risk; Health; Cd33; Osteoarthritis; Proteins
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Journal
Nature Communications
Quellenangaben
Volume: 12,
Issue: 1,
Article Number: 7042
Publisher
Nature Publishing Group
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Translational Genomics (ITG)
Grants
Medical Research Council
MRC Human Genetics Unit programme
UK Biobank Resource
Greek national funds through the Education and Lifelong Learning Operational Program of the National Strategic Reference Framework (NSRF)-Research Funding Program: Heracleitus II, Investing in knowledge society through the European Social Fund
European Union (European Social Fund-ESF)
European Research Council
Wellcome Trust
MRC Human Genetics Unit programme
UK Biobank Resource
Greek national funds through the Education and Lifelong Learning Operational Program of the National Strategic Reference Framework (NSRF)-Research Funding Program: Heracleitus II, Investing in knowledge society through the European Social Fund
European Union (European Social Fund-ESF)
European Research Council
Wellcome Trust