Abstract
Parkinson’s disease (PD) is the second most frequent neurogenic disease after Alzheimer’s disease. The clinical manifestations include mostly motor disorders, such as bradykinesia, myotonia, and static tremors. Since the cause of this pathological features remain unclear, there is currently no radical treatment for PD. Environmental and genetic factors are thought to contribute to the pathology of PD. To identify the genetic factors, some studies employed the Genome-Wide Association Studies (GWAS) method and detected certain genes closely related to PD. However, the functions of these gene mutants in the development of PD are unknown. Combining GWAS and expression Quantitative Trait Loci (eQTL) analysis, the biological meaning of mutation could be explained to some extent. Therefore, the present investigation used Summary data-based Mendelian Randomization (SMR) analysis to integrate of two PD GWAS datasets and four eQTL datasets with the objective of identifying casual genes. Using this strategy, we found six Single Nucleotide Polymorphism (SNP) loci which could cause the development of PD through altering the susceptibility gene expression, and three risk genes: Synuclein Alpha (SNCA), Mitochondrial Poly(A) Polymerase (MTPAP), and RP11-305E6.4. We proved the accuracy of results through case studies and inferred the functions of these genes in PD. Overall, this study provides insights into the genetic mechanism behind PD, which is crucial for the study of the development of this disease and its diagnosis and treatment.
Highlights
Parkinson’s disease (PD) is the second most common degenerative disorder of the nervous system
Since Single Nucleotide Polymorphism (SNP) are regarded as instrumental variables in Summary data-based Mendelian Randomization (SMR) analysis, we identified the overlapped SNPs between an expression Quantitative Trait Loci (eQTL) dataset and a Genome-Wide Association Studies (GWAS)
Since SNP is an instrumental variable, we searched for the same SNPs between a GWAS dataset and an eQTL dataset, generating eight new datasets (Table 1 and Supplementary Figures 1, 2)
Summary
Parkinson’s disease (PD) is the second most common degenerative disorder of the nervous system. As the incidence of this disease is strongly linked to age, approximately 1% of 65-year-olds has this disease, rising to 4–5% among aged 85 (Trinh and Farrer, 2013). The main clinical manifestations are involuntary limb tremor, bradykinesia, walking difficulty, and stiff limbs, and these symptoms become aggravated with time. This causes that PD patients are peculiarly prone to falls on routine activities. The incidence of falls could reach 40–70% (Kerr et al, 2010). The health and life of human beings, especially the elderly, are threatened by this disease
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