ArticleHuman mutation2009
Whole genome survey of coding SNPs reveals a reproducible pathway determinant of Parkinson disease.
Article in Human mutation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
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Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease.Human molecular genetics · 2013Pooled it
- Non-replication of association for six polymorphisms from meta-analysis of genome-wide association studies of Parkinson's disease: large-scale collaborative study.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2010Pooled it
- Genetic Variations of Vitamin A-Absorption and Storage-Related Genes, and Their Potential Contribution to Vitamin A Deficiency Risks Among Different Ethnic Groups.Frontiers in nutrition · 2022Review
- Evidence for an Interaction BetweenFrontiers in psychiatry · 2021Article
- Repulsive Guidance Molecule a (RGMa) Induces Neuropathological and Behavioral Changes That Closely Resemble Parkinson's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Loss of NEDD4 contributes to RTP801 elevation and neuron toxicity: implications for Parkinson's disease.Oncotarget · 2016Article
- The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?Brain research · 2015Review
- Enhanced ubiquitin-dependent degradation by Nedd4 protects against α-synuclein accumulation and toxicity in animal models of Parkinson's disease.Neurobiology of disease · 2014Article
- The role of inflammation in sporadic and familial Parkinson's disease.Cellular and molecular life sciences : CMLS · 2013Review
- Genetic variants and their interactions in disease risk prediction - machine learning and network perspectives.BioData mining · 2013Article
- Genome-wide gene-set analysis for identification of pathways associated with alcohol dependence.The international journal of neuropsychopharmacology · 2013Article
- Ubiquitin ligase Nedd4 promotes alpha-synuclein degradation by the endosomal-lysosomal pathway.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Shrunken methodology to genome-wide SNPs selection and construction of SNPs networks.BMC systems biology · 2010Article
- Kinesin light chain 1 gene haplotypes in three conformational diseases.Neuromolecular medicine · 2010Article
- Evidence for gender-specific transcriptional profiles of nigral dopamine neurons in Parkinson disease.PloS one · 2010Article
- Single-cell expression profiling of dopaminergic neurons combined with association analysis identifies pyridoxal kinase as Parkinson's disease gene.Annals of neurology · 2009Article
- Axon guidance and synaptic maintenance: preclinical markers for neurodegenerative disease and therapeutics.Trends in neurosciences · 2009Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
It is quickly becoming apparent that situating human variation in a pathway context is crucial to understanding its phenotypic significance. Toward this end, we have developed a general method for finding pathways associated with traits that control for pathway size. We have applied this method to a new whole genome survey of coding SNP variation in 187 patients afflicted with Parkinson disease (PD) and 187 controls. We show that our dataset provides an independent replication of the axon guidance association recently reported by Lesnick et al. [PLoS Genet 2007;3:e98], and also indicates that variation in the ubiquitin-mediated proteolysis and T-cell receptor signaling pathways may predict PD susceptibility. Given this result, it is reasonable to hypothesize that pathway associations are more replicable than individual SNP associations in whole genome association studies. However, this hypothesis is complicated by a detailed comparison of our dataset to the second recent PD association study by Fung et al. [Lancet Neurol 2006;5:911-916]. Surprisingly, we find that the axon guidance pathway does not rank at the very top of the Fung dataset after controlling for pathway size. More generally, in comparing the studies, we find that SNP frequencies replicate well despite technologically different assays, but that both SNP and pathway associations are globally uncorrelated across studies. We thus have a situation in which an association between axon guidance pathway variation and PD has been found in 2 out of 3 studies. We conclude by relating this seeming inconsistency to the molecular heterogeneity of PD, and suggest future analyses that may resolve such discrepancies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.