JAMA Sub-Journal: What are the pathogenic genes for Parkinson's disease?

Parkinson's disease (PD) is the world's second-largest neurodegenerative disease characterized by slow movement, limb stiffness and tremors.
people with PD may also have cognitive and behavioral problems, such as dementia, which is fairly common in severe patients, and more than a third of cases can also cause severe depressive disorder and anxiety.
other possible symptoms include perception, sleep, and emotional problems.
The GWAS study found more than 40 genes associated with a significant risk of Parkinson's disease.
, however, these studies are limited to narrowing the risk of Parkinson's disease to genomic regions that contain several candidate genes.
the causal genes behind each gene and the mechanisms they place at risk for Parkinson's disease remain unclear.
these problems can be solved by using quantitative genotype (QTL) datasets, which describe the association of individual genotypes with gene expression, shearing, or methylation.
studies have shown that GWAS risk variation may be associated with gene expression or shearing.
with advances in bio-informational tools, combined with QTL, allows us to conduct a more thorough study of the genes screened by GTAS.
To this end, a team of experts from University College London used Parkinson's disease-related GWAS and other data sets to systematically review all known Parkinson's disease risk site to reveal the genes and mechanisms associated with PD risk of GTA risk variation.
results were published in the latest journal JAMA Neurology.
The genetic association study used the bioinsynomic tool Coloc and the Full Transcription Group Association Study (TWAS) to combine PD case control GWAS data, gene expression data (from Brainac, genotype-tissue expression (GTEx) and CommonMind) and methylation data (from PD brain samples in the UK) to reveal hypothetical gene expression and shearing mechanisms associated with GWAS signals for Parkinson's disease.
candidate genes are further ocminated using cell type specificity, weighted gene co-expression networks, and weighted protein-protein interaction (PPI) networks.
observations are based on a priori hypothesis that some of the potential PD gene expression points, which alter the risk of Parkinson's disease by altering expression, shearing, or methylation.
analysis of gene level expression showed that five genes in the GTEx and Braineac expression datasets (WDR6, CD38, GPNMB, RAB29, and MEM163) were validated in Coloc and TWAS.
six other genes (ZRANB3, PCGF3, NEK1, NUPL2, GALC, and TSB) show evidence of disease-related shear effects.
of cell type specificity showed that the expression of genes in glials (e.g. small glial cells, less protrusive glial cells, etc.) was generally more common than in neurons.
Weighted gene co-expression on the GTEx dataset shows that NUPL2 is a key gene in three modules, involving the decomposition and metabolism process associated with protein ubibinization and the breakdown and metabolism of ubibin-dependent proteins in volt-isolation, tail-like nuclei, and crust nuclei.
addition, TMEM163 in the forehead and ZRANB3 in the tail core are key genes in different brain regions, respectively, involved in the communication of their cell signals.
PPI and random network simulations show that the candidate gene has a significant effect on the known PD Mendel effect.
, the results show that the above candidate genes and related path pathps are closely related to the incidence of PD.
references: Category of Candidate Parkinson Disease Genes by Integrating Genome-Wide Association Study, Expression, and EpiGenetic Data Sets. JAMA Neurol (2021). doi:10.1001/jamaneurol.2020.5257MedSci Original Source: MedSci Original Copyright Notice: All notes on this website "Source: Met Medical" or "Source: MedSci Original" text, images and audio and video materials, copyrights are owned by Metz Medicine, without authorization, no media, website or individual may reproduce, authorized to reproduce with the words "Source: Mets Medicine".
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