Mapping the serum proteome to neurological diseases using whole genome sequencing

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-rel...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications Vol. 12; no. 1; pp. 7042 - 12
Main Authors: Png, Grace, Barysenka, Andrei, Repetto, Linda, Navarro, Pau, Shen, Xia, Pietzner, Maik, Wheeler, Eleanor, Wareham, Nicholas J., Langenberg, Claudia, Tsafantakis, Emmanouil, Karaleftheri, Maria, Dedoussis, George, Mälarstig, Anders, Wilson, James F., Gilly, Arthur, Zeggini, Eleftheria
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 02.12.2021
Nature Publishing Group
Nature Portfolio
Subjects:
45
45/23
45/43
631/208/205/2138
631/208/366
692/53/2423
692/699/375
82/1
82/80
Alzheimer Disease - blood
Alzheimer Disease - diagnosis
Alzheimer Disease - genetics
Alzheimer Disease - pathology
Alzheimer's disease
Biomarkers
Biomarkers - blood
Cohort Studies
Gene Expression
Gene mapping
Gene Ontology
Gene sequencing
Genetic Predisposition to Disease
Genome, Human
Genomes
Humanities and Social Sciences
Humans
Membrane Glycoproteins - blood
Membrane Glycoproteins - genetics
Mendelian Randomization Analysis
Mental disorders
Molecular Sequence Annotation
Movement disorders
multidisciplinary
Neurodegenerative diseases
Neurological diseases
Neurological disorders
Parkinson Disease - blood
Parkinson Disease - diagnosis
Parkinson Disease - genetics
Parkinson Disease - pathology
Parkinson's disease
Proteins
Proteome - genetics
Proteome - metabolism
Proteomes
Quantitative Trait Loci
Scavenger Receptors, Class A - blood
Scavenger Receptors, Class A - genetics
Schizophrenia
Schizophrenia - blood
Schizophrenia - diagnosis
Schizophrenia - genetics
Schizophrenia - pathology
Science
Science (multidisciplinary)
Serum proteins
Sialic Acid Binding Ig-like Lectin 3 - blood
Sialic Acid Binding Ig-like Lectin 3 - genetics
Therapeutic targets
Whole Genome Sequencing
ISSN:2041-1723, 2041-1723
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Serum proteins are easily accessible biomarkers and drug targets. Here, the authors use whole genome sequencing data to describe the genetic architecture of neurologically-relevant serum proteins and establish causal protein-neurological disease relationships.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-27387-1