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Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders
- Source :
- Nature neuroscience
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Understanding the tissue-specific genetic controls of protein levels is essential to uncover mechanisms of post-transcriptional gene regulation. In this study, we generated a genomic atlas of protein levels in three tissues relevant to neurological disorders (brain, cerebrospinal fluid and plasma) by profiling thousands of proteins from participants with and without Alzheimer’s disease. We identified 274, 127 and 32 protein quantitative trait loci (pQTLs) for cerebrospinal fluid, plasma and brain, respectively. cis-pQTLs were more likely to be tissue shared, but trans-pQTLs tended to be tissue specific. Between 48.0% and 76.6% of pQTLs did not co-localize with expression, splicing, DNA methylation or histone acetylation QTLs. Using Mendelian randomization, we nominated proteins implicated in neurological diseases, including Alzheimer’s disease, Parkinson’s disease and stroke. This first multi-tissue study will be instrumental to map signals from genome-wide association studies onto functional genes, to discover pathways and to identify drug targets for neurological diseases. Yang et al. generated a genomic atlas of protein levels in brain, cerebrospinal fluid and plasma and used human genetics approaches to identify proteins implicated in neurological diseases as well as druggable targets.
- Subjects :
- Male
Proteomics
Proteome
Quantitative Trait Loci
Disease
Quantitative trait locus
Bioinformatics
Article
Plasma
Alzheimer Disease
Mendelian randomization
Humans
Aged
Cerebrospinal Fluid
Regulation of gene expression
biology
General Neuroscience
Brain
Middle Aged
Human genetics
High-Throughput Screening Assays
Histone
Gene Expression Regulation
DNA methylation
biology.protein
Female
Neuroscience
Subjects
Details
- ISSN :
- 15461726 and 10976256
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Nature Neuroscience
- Accession number :
- edsair.doi.dedup.....a8a5a02806a94c7da8db1f97ff3d0f00