Dataset Information

Genetic variation of CHRNA4 does not modulate attention in Parkinson's disease.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder, characterised by cognitive decline and attentional impairment. Recently, variation in CHRNA4 (rs1044396) has been shown to affect visual and auditory function, affecting speed and attention, in healthy adults. An association between CHRNA4 variation and PD has not been shown. To determine the link between CHRNA4 variation and attentional deficit in PD. A genotype-phenotype correlation between the common CHRNA4:rs1044396 variant and several baseline parameters of attention was carried out in a large cohort of PD cases (n=222) and controls (n=159). We identified significant associations to measures of attention in PD patients compared to controls. However, we found no significant link to CHRNA4:rs1044396 genotypes to baseline attention variables in PD or in controls. We conclude that CHRNA4:rs1044396 genotypes do not significantly influence the attentional deficit found in PD patients. Contrary to previous studies, we also found no significant influence in healthy age-matched controls.

SUBMITTER: Hudson G

PROVIDER: S-EPMC4038490 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Genetic variation of CHRNA4 does not modulate attention in Parkinson's disease.

Hudson Gavin G Stutt Andrea A Eccles Martin M Robinson Louise L Allcock Liesl M LM Wesnes Keith A KA Chinnery Patrick F PF Burn David J DJ

Neuroscience letters 20100520 2

Parkinson's disease (PD) is a neurodegenerative disorder, characterised by cognitive decline and attentional impairment. Recently, variation in CHRNA4 (rs1044396) has been shown to affect visual and auditory function, affecting speed and attention, in healthy adults. An association between CHRNA4 variation and PD has not been shown. To determine the link between CHRNA4 variation and attentional deficit in PD. A genotype-phenotype correlation between the common CHRNA4:rs1044396 variant and severa ...[more]

PMID: 20493238

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Project description:BackgroundMitochondrial dysfunction plays a key role in PD, but the underlying molecular mechanisms remain unresolved. We hypothesized that the disruption of mitochondrial function in PD is primed by rare, protein-altering variation in nuclear genes controlling mitochondrial structure and function.ObjectiveThe objective of this study was to assess whether genetic variation in genes associated with mitochondrial function influences the risk of idiopathic PD.MethodsWe employed whole-exome sequencing data from 2 independent cohorts of clinically validated idiopathic PD and controls, the Norwegian ParkWest cohort (n = 411) and the North American Parkinson's Progression Markers Initiative (n = 640). We applied burden-based and variance-based collapsing methods to assess the enrichment of rare, nonsynonymous, and damaging genetic variants on genes, exome-wide, and on a comprehensive set of mitochondrial pathways, defined as groups of genes controlling specific mitochondrial functions.ResultsUsing the sequence kernel association test, we detected a significant polygenic enrichment of rare, nonsynonymous variants in the gene-set encoding the pathway of mitochondrial DNA maintenance. Notably, this was the strongest association in both cohorts and survived multiple testing correction (ParkWest P = 6.3 × 10-3 , Parkinson's Progression Markers Initiative P = 6.9 × 10-5 , metaanalysis P = 3.2 × 10-6 ).ConclusionsOur results show that the enrichment of rare inherited variation in the pathway controlling mitochondrial DNA replication and repair influences the risk of PD. We propose that this polygenic enrichment contributes to the impairment of mitochondrial DNA homeostasis, thought to be a key mechanism in the pathogenesis of PD, and explains part of the disorder's "missing heritability." © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Project description:Background:The phospholipase A2 Group 6 (PLA2G6, also known as PLA2, PARK14, and iPLA2) gene encodes a group VIA calcium-independent phospholipase A2. Genetic polymorphism of PLA2G6 has been indicated to be involved in conferring susceptibility for Parkinson's disease (PD), whereas conclusive results have not been obtained. Thus, we intended to conduct a systematic review to determine if PLA2G6 genetic variation confers a greater susceptibility to PD. Methods:All case-control studies that investigated the association of the PLA2G6 polymorphisms with the risk of PD published before 15 July 2018 were included. The literature was comprehensively searched and identified in five English databases (EBSCO, Pubmed, OVID, EMBASE and ISI Web of Knowledge) and four Chinese databases (Wanfang database, Chinese Biomedical Literature Database, China Academic Journals Database and VIP database). We performed analyses of study characteristics, heterogeneity, and forest plot in analyses analogous to dominant, codominant and additive models with the pooled odds ratio (OR) in fixed- or random-effects models as the measure of association. Results:A total of 664 potentially relevant studies were retrieved with the initial search, of which eight studies fulfilled the inclusion criteria, and included 2,779 PD patients and 3,291 control participants,. Among all the reported 27 genetic variants, 15 single nucleotide polymorphisms (SNPs) were present only in patients, and only five available SNPs (rs2267369, rs140758033, c.1959T>A (Gly653Gly), rs76718524, rs199935023) were pooled in the meta-analysis. However, there was no evidence for a significant association between the five SNPs and PD risk in dominant, codominant and allele models, suggesting a lack of association between PLA2G6 genetic variation and PD susceptibility. Conclusion:The present study assessed the association of PLA2G6 genetic polymorphism with the risk PD, and the result strongly demonstrates that PLA2G6 polymorphism is not associated with PD susceptibility.

Dataset Information

Genetic variation of CHRNA4 does not modulate attention in Parkinson's disease.

Publications

Genetic variation of CHRNA4 does not modulate attention in Parkinson's disease.

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