ArticleMovement disorders : official journal of the Movement Disorder Society2019
The endocytic membrane trafficking pathway plays a major role in the risk of Parkinson's disease.
Article in Movement disorders : official journal of the Movement Disorder Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies.The Lancet. Neurology · 2019Pooled it
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- Distinct and combined interferon-ɑ/β-receptor-1 loss in neurons and astrocytes disrupt brain energy metabolism and drive Parkinsonian dementia.Journal of biomedical science · 2026Article
- The Relationship of Peripheral Glycoprotein Nonmetastatic Melanoma Protein B and Parkinson's Disease: Insights From a Mendelian Randomization Study.International journal of genomics · 2026Article
- Bidirectional Effects of Sleep Deprivation Associated with Parkinson's Disease on Behavior, Oxidative Stress, and Energy Metabolism in Male and Female Rats.Molecular neurobiology · 2025Article
- Intracellular and Extracellular Vesicle miRNA Signatures in Human iPSC-Derived Neural Stem Cells and Floor Plate Progenitors.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- PLEKHM1 Overexpression Impairs Autophagy and Exacerbates Neurodegeneration in rAAV-α-Synuclein Mice.Cells · 2025Article
- Low-frequency genetic variants in GAK enhance Golgi function and protect against Parkinson's disease.medRxiv : the preprint server for health sciences · 2025Article
- Drug discovery and development for Parkinson's disease: are preclinical models good enough?Frontiers in aging neuroscience · 2025Review
- A candidate loss-of-function variant in SGIP1 causes synaptic dysfunction and recessive parkinsonism.Cell reports. Medicine · 2024Article
- LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting.Trends in molecular medicine · 2024Review
- Article
- Lysosomal and synaptic dysfunction markers in longitudinal cerebrospinal fluid of de novo Parkinson's disease.NPJ Parkinson's disease · 2024Article
- Cell biology of Parkinson's disease: Mechanisms of synaptic, lysosomal, and mitochondrial dysfunction.Current opinion in neurobiology · 2024Review
- Deep sequencing of proteotoxicity modifier genes uncovers a Presenilin-2/beta-amyloid-actin genetic risk module shared among alpha-synucleinopathies.bioRxiv : the preprint server for biology · 2024Article
- Lysosomal polygenic risk is associated with the severity of neuropathology in Lewy body disease.Brain : a journal of neurology · 2023Article
- Recent advances in novel mutation genes of Parkinson's disease.Journal of neurology · 2023Review
- Identification of mitophagy-related biomarkers and immune infiltration in major depressive disorder.BMC genomics · 2023Article
- Loss of NDR1/2 kinases impairs endomembrane trafficking and autophagy leading to neurodegeneration.Life science alliance · 2023Article
- Precision Medicine in Parkinson's Disease: From Genetic Risk Signals to Personalized Therapy.Brain sciences · 2022Review
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Abstract
backgroundPD is a complex polygenic disorder. In recent years, several genes from the endocytic membrane-trafficking pathway have been suggested to contribute to disease etiology. However, a systematic analysis of pathway-specific genetic risk factors is yet to be performed.
objectivesTo comprehensively study the role of the endocytic membrane-trafficking pathway in the risk of PD.
methodsLinkage disequilibrium score regression was used to estimate PD heritability explained by 252 genes involved in the endocytic membrane-trafficking pathway including genome-wide association studies data from 18,869 cases and 22,452 controls. We used pathway-specific single-nucleotide polymorphisms to construct a polygenic risk score reflecting the cumulative risk of common variants. To prioritize genes for follow-up functional studies, summary-data based Mendelian randomization analyses were applied to explore possible functional genomic associations with expression or methylation quantitative trait loci.
resultsThe heritability estimate attributed to endocytic membrane-trafficking pathway was 3.58% (standard error = 1.17). Excluding previously nominated PD endocytic membrane-trafficking pathway genes, the missing heritability was 2.21% (standard error = 0.42). Random heritability simulations were estimated to be 1.44% (standard deviation = 0.54), indicating that the unbiased total heritability explained by the endocytic membrane-trafficking pathway was 2.14%. Polygenic risk score based on endocytic membrane-trafficking pathway showed a 1.25 times increase of PD risk per standard deviation of genetic risk. Finally, Mendelian randomization identified 11 endocytic membrane-trafficking pathway genes showing functional consequence associated to PD risk.
conclusionsWe provide compelling genetic evidence that the endocytic membrane-trafficking pathway plays a relevant role in disease etiology. Further research on this pathway is warranted given that critical effort should be made to identify potential avenues within this biological process suitable for therapeutic interventions. © 2019 International Parkinson and Movement Disorder Society.
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