Replication of association between ELAVL4 and Parkinson disease: the GenePD study.
Ontology highlight
ABSTRACT:
SUBMITTER: DeStefano AL
PROVIDER: S-EPMC2716559 | biostudies-literature | 2008 Aug
REPOSITORIES: biostudies-literature
Publications
Replication of association between ELAVL4 and Parkinson disease: the GenePD study.
DeStefano Anita L AL Latourelle Jeanne J Lew Mark F MF Suchowersky Oksana O Klein Christine C Golbe Lawrence I LI Mark Margery H MH Growdon John H JH Wooten G Fredrick GF Watts Ray R Guttman Mark M Racette Brad A BA Perlmutter Joel S JS Marlor Lynn L Shill Holly A HA Singer Carlos C Goldwurm Stefano S Pezzoli Gianni G Saint-Hilaire Marie H MH Hendricks Audrey E AE Gower Adam A Williamson Sally S Nagle Michael W MW Wilk Jemma B JB Massood Tiffany T Huskey Karen W KW Baker Kenneth B KB Itin Ilia I Litvan Irene I Nicholson Garth G Corbett Alastair A Nance Martha M Drasby Edward E Isaacson Stuart S Burn David J DJ Chinnery Patrick F PF Pramstaller Peter P PP Al-Hinti Jomana J Moller Anette T AT Ostergaard Karen K Sherman Scott J SJ Roxburgh Richard R Snow Barry B Slevin John T JT Cambi Franca F Gusella James F JF Myers Richard H RH
Human genetics 20080629 1
Genetic variants in embryonic lethal, abnormal vision, Drosophila-like 4 (ELAVL4) have been reported to be associated with onset age of Parkinson disease (PD) or risk for PD affection in Caucasian populations. In the current study we genotyped three single nucleotide polymorphisms in ELAVL4 in a Caucasian study sample consisting of 712 PD patients and 312 unrelated controls from the GenePD study. The minor allele of rs967582 was associated with increased risk of PD (odds ratio = 1.46, nominal P ...[more]
Similar Datasets
Project description:BackgroundMicrotubule-associated protein tau (MAPT) has been associated with several neurodegenerative disorders including forms of parkinsonism and Parkinson disease (PD). We evaluated the association of the MAPT region with PD in a large cohort of familial PD cases recruited by the GenePD Study. In addition, postmortem brain samples from patients with PD and neurologically normal controls were used to evaluate whether the expression of the 3-repeat and 4-repeat isoforms of MAPT, and neighboring genes Saitohin (STH) and KIAA1267, are altered in PD cerebellum.MethodsTwenty-one single-nucleotide polymorphisms (SNPs) in the region of MAPT on chromosome 17q21 were genotyped in the GenePD Study. Single SNPs and haplotypes, including the H1 haplotype, were evaluated for association to PD. Relative quantification of gene expression was performed using real-time RT-PCR.ResultsAfter adjusting for multiple comparisons, SNP rs1800547 was significantly associated with PD affection. While the H1 haplotype was associated with a significantly increased risk for PD, a novel H1 subhaplotype was identified that predicted a greater increased risk for PD. The expression of 4-repeat MAPT, STH, and KIAA1267 was significantly increased in PD brains relative to controls. No difference in expression was observed for 3-repeat MAPT.ConclusionsThis study supports a role for MAPT in the pathogenesis of familial and idiopathic Parkinson disease (PD). Interestingly, the results of the gene expression studies suggest that other genes in the vicinity of MAPT, specifically STH and KIAA1267, may also have a role in PD and suggest complex effects for the genes in this region on PD risk.
| S-EPMC2654275 | biostudies-literature
Project description:Mutations in GIGYF2 have recently been described as causative of Parkinson's disease in Europeans. In an attempt to replicate these results in independent populations, we sequenced the entire coding region of GIGYF2 in a large series of Portuguese and North American samples. We report the finding of two of the previously published mutations in neurologically normal Control individuals. This suggests that mutations in GIGYF2 are not strongly related to the development of the disease in either of these populations.
| S-EPMC2638775 | biostudies-literature
Project description:Parkinson disease (PD) is a late-onset neurodegenerative disorder. The mean age at onset is 61 years, but the disease can range from juvenile cases to cases in the 8th or 9th decade of life. The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD. We have performed a genomewide linkage analysis using variance-component methodology to identify genes influencing age at onset of PD in a population of affected relatives (mainly affected sibling pairs) participating in the GenePD study. Four chromosomal loci showed suggestive evidence of linkage: chromosome 2p (maximum multipoint LOD [MaxLOD] = 2.08), chromosome 9q (MaxLOD = 2.00), chromosome 20 (MaxLOD = 1.82), and chromosome 21 (MaxLOD = 2.21). The 2p and 9q locations that we report here have previously been reported as loci influencing PD affection status. Association between PD age at onset and allele 174 of marker D2S1394, located on 2p13, was observed in the GenePD sample (P=.02). This 174 allele is common to the PD haplotype observed in two families that show linkage to PARK3 and have autosomal dominant PD, which suggests that this allele may be in linkage disequilibrium with a mutation influencing PD susceptibility or age at onset of PD.
| S-EPMC447587 | biostudies-literature
Project description:Fatigue is a disabling non-motor symptom in Parkinson disease (PD). We investigated the relationship between autonomic dysfunction and fatigue in PD while accounting for possible confounding factors.29 subjects with PD (8F/21M; mean age 61.6±5.9; mean disease duration 4.8±3.0years), underwent clinical assessment and completed several non-motor symptom questionnaires, including a modified version of the Mayo Clinic Composite Autonomic Symptom Score (COMPASS) scale and the Fatigue Severity Scale (FSS).The mean modified COMPASS was 21.6±14.2 (range 1.7-44.2) and the mean FSS score was 3.3±1.6 (range 1.0-6.7). There was a significant bivariate relationship between the modified COMPASS and FSS scores (R=0.69, P<0.0001). Stepwise regression analysis was used to assess the specificity of the association between the modified COMPASS and FSS scores while accounting for possible confounder effects from other variables that were significantly associated with autonomic dysfunction. Results showed that the modified COMPASS (R2=0.52, F=28.4, P<0.0001) was highly associated with fatigue, followed by ESS (R2=0.13, F=8.4, P=0.008) but no other co-variates. Post-hoc analysis exploring the association between the different modified COMPASS autonomic sub-domain scores and FSS scores found significant regressor effects for the orthostatic intolerance (R2=0.45, F=21.2, P<0.0001) and secretomotor sub-domains (R2=0.09, F=4.8, P=0.04) but not for other autonomic sub-domains.Autonomic dysfunction, in particular orthostatic intolerance, is highly associated with fatigue in PD.
| S-EPMC5536106 | biostudies-literature
Project description:Mutations in the ?-synuclein gene (SNCA) cause autosomal dominant forms of Parkinson's disease, but the substantial risk conferred by this locus to the common sporadic disease has only recently emerged from genome-wide association studies.We genotyped a prioritized noncoding variant in SNCA intron 4 in 344 patients with Parkinson's disease and 275 controls from the longitudinal Harvard NeuroDiscovery Center Biomarker Study.The common minor allele of rs2736990 was associated with elevated disease susceptibility (odds ratio, 1.40; P = .0032).This result increases confidence in the notion that in many clinically well-characterized patients, genetic variation in SNCA contributes to "sporadic" disease.
| S-EPMC3337217 | biostudies-literature
Project description:BACKGROUND:Age at onset in Parkinson disease (PD) is a highly heritable quantitative trait for which a significant genetic influence is supported by multiple segregation analyses. Because genes associated with onset age may represent invaluable therapeutic targets to delay the disease, we sought to identify such genetic modifiers using a genomewide association study in familial PD. There have been previous genomewide association studies (GWAS) to identify genes influencing PD susceptibility, but this is the first to identify genes contributing to the variation in onset age. METHODS:Initial analyses were performed using genotypes generated with the Illumina HumanCNV370Duo array in a sample of 857 unrelated, familial PD cases. Subsequently, a meta-analysis of imputed SNPs was performed combining the familial PD data with that from a previous GWAS of 440 idiopathic PD cases. The SNPs from the meta-analysis with the lowest p-values and consistency in the direction of effect for onset age were then genotyped in a replication sample of 747 idiopathic PD cases from the Parkinson Institute Biobank of Milan, Italy. RESULTS:Meta-analysis across the three studies detected consistent association (p < 1 x 10(-5)) with five SNPs, none of which reached genomewide significance. On chromosome 11, the SNP with the lowest p-value (rs10767971; p = 5.4 x 10(-7)) lies between the genes QSER1 and PRRG4. Near the PARK3 linkage region on chromosome 2p13, association was observed with a SNP (rs7577851; p = 8.7 x 10(-6)) which lies in an intron of the AAK1 gene. This gene is closely related to GAK, identified as a possible PD susceptibility gene in the GWAS of the familial PD cases. CONCLUSION:Taken together, these results suggest an influence of genes involved in endocytosis and lysosomal sorting in PD pathogenesis.
| S-EPMC2758866 | biostudies-literature
Project description:We performed a two-tiered, whole-genome association study of Parkinson disease (PD). For tier 1, we individually genotyped 198,345 uniformly spaced and informative single-nucleotide polymorphisms (SNPs) in 443 sibling pairs discordant for PD. For tier 2a, we individually genotyped 1,793 PD-associated SNPs (P<.01 in tier 1) and 300 genomic control SNPs in 332 matched case-unrelated control pairs. We identified 11 SNPs that were associated with PD (P<.01) in both tier 1 and tier 2 samples and had the same direction of effect. For these SNPs, we combined data from the case-unaffected sibling pair (tier 1) and case-unrelated control pair (tier 2) samples and employed a liberalization of the sibling transmission/disequilibrium test to calculate odds ratios, 95% confidence intervals, and P values. A SNP within the semaphorin 5A gene (SEMA5A) had the lowest combined P value (P=7.62 x 10(-6)). The protein encoded by this gene plays an important role in neurogenesis and in neuronal apoptosis, which is consistent with existing hypotheses regarding PD pathogenesis. A second SNP tagged the PARK11 late-onset PD susceptibility locus (P=1.70 x 10(-5)). In tier 2b, we also selected for genotyping additional SNPs that were borderline significant (P<.05) in tier 1 but that tested a priori biological and genetic hypotheses regarding susceptibility to PD (n=941 SNPs). In analysis of the combined tier 1 and tier 2b data, the two SNPs with the lowest P values (P=9.07 x 10(-6); P=2.96 x 10(-5)) tagged the PARK10 late-onset PD susceptibility locus. Independent replication across populations will clarify the role of the genomic loci tagged by these SNPs in conferring PD susceptibility.
| S-EPMC1271381 | biostudies-literature
Project description:BACKGROUND:Recent data showed that melanoma was more common among patients with Parkinson disease than individuals without Parkinson disease and vice versa. It has been hypothesized that these two diseases may share common genetic and environmental risk factors. METHODS:We evaluated the association between single-nucleotide polymorphisms (SNP) selected on the basis of recent genome-wide association studies (GWAS) on Parkinson disease risk and the risk of melanoma using 2,297 melanoma cases and 6,651 controls. RESULTS:The Parkinson disease SNP rs156429 in the chromosome 7p15 region was nominally associated with melanoma risk with P value of 0.04, which was not significant after the Bonferroni correction for multiple comparisons. No association was observed between the remaining 31 Parkinson disease SNPs and the risk of melanoma. The genetic score based on the number of Parkinson disease risk allele was not associated with melanoma risk [OR for the highest genetic score quartile (30-35) vs. the lowest (15-20), 1.13, 95% confidence interval (CI), 0.47-2.70]. CONCLUSION:The Parkinson disease SNPs identified in published GWAS do not seem to play an important role in melanoma development. IMPACT:The Parkinson disease susceptibility loci discovered by GWAS contribute little to the observed epidemiologic association between the Parkinson disease and melanoma.
| S-EPMC3253945 | biostudies-literature
Project description:BackgroundIgG-class autoantibodies to N-Methyl-D-Aspartate (NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis. Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results. We measured NMDA antibodies in a large, well phenotyped sample of Parkinson patients without and with cognitive impairment (n = 296) and controls (n = 295) free of neuropsychiatric disease. Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.MethodsNMDA antibodies were analysed in the serum of patients and controls using well established validated assays. We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.ResultsThe frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients (13%) than in controls (22%) and higher than in previous studies in both groups. NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment, nor with quantitative indicators of disease severity and cognitive impairment. A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.ConclusionIt is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g. to Parkinson disease with dementia, while NMDA IgG antibodies define a separate disease of its own.
| S-EPMC6446289 | biostudies-literature
Project description:Backward walking often occurs in everyday life. It is more complex than forward walking and is associated with decreased coordination. However, it is unclear if a reduced backward walking performance is associated with impaired cognition. This could be particularly relevant as gait and cognitive deficits commonly occur in Parkinson's disease. The objective of this systematic review was to synthesize the evidence on the association between backward walking and cognition in persons with Parkinson's disease. The electronic databases PubMed and Web of Science were systematically searched, and the quality of eligible studies was assessed. Two studies met the inclusion criteria, but study protocols, investigated population, and outcome measures differed substantially. One study showed lower backward walking speed in patients with Parkinson's disease with poorer attention test performances. The second study showed a weak correlation between executive cognitive functions and backward walking speed. Given the low number of studies, the heterogenous study design, and the inconsistent results, the present review highlights the need to further investigate the association between backward walking and cognition in patients with Parkinson's disease.
| S-EPMC9566137 | biostudies-literature