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Prioritizing Parkinson’s disease genes using population-scale transcriptomic data
- Source :
- Nature Communications, Vol 10, Iss 1, Pp 1-10 (2019), Nature Communications
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- Genome-wide association studies (GWAS) have identified over 41 susceptibility loci associated with Parkinson’s Disease (PD) but identifying putative causal genes and the underlying mechanisms remains challenging. Here, we leverage large-scale transcriptomic datasets to prioritize genes that are likely to affect PD by using a transcriptome-wide association study (TWAS) approach. Using this approach, we identify 66 gene associations whose predicted expression or splicing levels in dorsolateral prefrontal cortex (DLFPC) and peripheral monocytes are significantly associated with PD risk. We uncover many novel genes associated with PD but also novel mechanisms for known associations such as MAPT, for which we find that variation in exon 3 splicing explains the common genetic association. Genes identified in our analyses belong to the same or related pathways including lysosomal and innate immune function. Overall, our study provides a strong foundation for further mechanistic studies that will elucidate the molecular drivers of PD.<br />GWAS have identified over 41 susceptibility loci for Parkinson’s disease (PD). Here, the authors integrate PD GWAS summary statistics with transcriptome data from monocytes and DLFPC tissue in a TWAS approach and find 66 significant associations with PD risk highlighting lysosomal and innate immune functions.
- Subjects :
- 0301 basic medicine
Genotype
Science
Population
General Physics and Astronomy
Genomics
Genome-wide association study
02 engineering and technology
Disease
Computational biology
Biology
Polymorphism, Single Nucleotide
General Biochemistry, Genetics and Molecular Biology
Article
Transcriptome
03 medical and health sciences
Exon
0302 clinical medicine
Risk Factors
Databases, Genetic
Humans
Genetic Predisposition to Disease
education
lcsh:Science
Gene
030304 developmental biology
Genetic association
0303 health sciences
education.field_of_study
Multidisciplinary
Parkinson Disease
General Chemistry
021001 nanoscience & nanotechnology
Immunity, Innate
030104 developmental biology
Gene Expression Regulation
RNA splicing
lcsh:Q
0210 nano-technology
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....3fbc89f0485e9b3f24f991c3ee55be98