Mapping the serum proteome to neurological diseases using whole genome sequencing.
Alzheimer Disease
/ blood
Biomarkers
/ blood
Cohort Studies
Gene Expression
Gene Ontology
Genetic Predisposition to Disease
Genome, Human
Humans
Membrane Glycoproteins
/ blood
Mendelian Randomization Analysis
Molecular Sequence Annotation
Parkinson Disease
/ blood
Proteome
/ genetics
Quantitative Trait Loci
Scavenger Receptors, Class A
/ blood
Schizophrenia
/ blood
Sialic Acid Binding Ig-like Lectin 3
/ blood
Whole Genome Sequencing
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 12 2021
02 12 2021
Historique:
received:
15
04
2021
accepted:
11
11
2021
entrez:
3
12
2021
pubmed:
4
12
2021
medline:
5
1
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34857772
doi: 10.1038/s41467-021-27387-1
pii: 10.1038/s41467-021-27387-1
pmc: PMC8640022
doi:
Substances chimiques
Biomarkers
0
CD33 protein, human
0
GPNMB protein, human
0
MSR1 protein, human
0
Membrane Glycoproteins
0
Proteome
0
Scavenger Receptors, Class A
0
Sialic Acid Binding Ig-like Lectin 3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7042Subventions
Organisme : Medical Research Council
ID : U. MC_UU_00007/10
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_13046
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_U127592696
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 098051
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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