Replication of MAPT and SNCA, but not PARK16‐18, as susceptibility genes for Parkinson's disease

Mata, Ignacio; Yearout, Dora; Álvarez, Victoria; Coto, Eliécer; Mena, Lorena de; Ribacoba, René; Lorenzo‐Betancor, Oswaldo; Samaranch, Lluı́s; Pástor, Pau; Cervantes, Sebastián; Infante, Jon; García‐Gorostiaga, Inés; Sierra, María; Combarros, Onofre; Snapinn, Katherine W.; Edwards, Karen L.; Zabetian, Cyrus P.

doi:10.1002/mds.23642

Cited by 69 publications

(49 citation statements)

References 24 publications

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“…Our results were consistent with several studies in Asian population (Satake et al, 2009;Tan et al, 2010). However, similar studies including Europeans showed that this locus was not associated with the occurrence of PD (Ramirez et al, 2011;Mata et al, 2011), further suggesting that the presence of polymorphic loci differs among various races.…”

Section: Haplotype Analysis Of Park16supporting

confidence: 93%

Association between PARK16 gene polymorphisms and susceptibility of Parkinson's disease in a Chinese population

Xia¹,

Luo²,

Li³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Recent genome-wide association studies identified 11 risk loci in different populations of familial and sporadic Parkinson's disease (PD) patients. Few loci have been verified in different European and Asian populations. We also validated 2 new single-nucleotide polymorphisms, rs947211 and rs823144, in PARK16 to explore their association with susceptibility to PD in the Xinjiang Uygur and Han populations. This case-control study included 312 PD patients (130 Uygur and 182 Han) and 359 control subjects (179 Uygur and 180 Han). Polymerase chain reaction-restriction fragment length polymorphism analysis and DNA sequencing were used to detect the rs947211 and rs823144 polymorphism in the PARK16 gene between the Xinjiang Uygur and Han populations. Frequencies of the A allele and AA genotype (42.1 and 15.7%, respectively) of rs947211 in PD patients were significantly lower than those in the control group (54.7 and 28.7%, respectively, P < 0.01). A allele and AA genotype frequencies of rs823144 were 56.8 and 31.8% in the PD patients group and were 54.1 and 29.3% in the control group; no significant difference was found (P > 0.05). In both the Han and Uygur groups, the rs947211 polymorphism was associated with PD. Haplotype analysis also indicated that the A-A and G-A haplotypes were associated with PD. We found that the rs947211 polymorphism may be a susceptibility marker for PD in the Chinese population; the A-A and G-A haplotypes may be a protective factor and a risk factor, respectively, for PD in the Chinese population.

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Section: Haplotype Analysis Of Park16supporting

confidence: 93%

Association between PARK16 gene polymorphisms and susceptibility of Parkinson's disease in a Chinese population

Xia¹,

Luo²,

Li³

et al. 2015

Genet. Mol. Res.

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“…[3][4][5][6][7][8][9][10][11] Consistent and reproducible association signals were confirmed in ␣-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2), and microtubule-associated protein tau (MAPT), thus underscoring the importance of these 3 genes in the pathophysiology of the common sporadic forms of PD. [3][4][5][6][7][8][9][10]12 In addition to that, different studies have provided some evidence for an association for BST1, GAK, and HLA-DRB5 with PD. 6 -9,13 A recently published GWAS meta-analysis in PD increased the number of identified PD genetic loci to 11. 14 This study reported significant between-study heterogeneity for some of the 11 genetic loci 14 even though data were restricted to Caucasian descent populations.…”

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confidence: 97%

Large-scale replication and heterogeneity in Parkinson disease genetic loci

Sharma¹,

Ioannidis²,

Aasly³

et al. 2012

Neurology

121

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Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Methods:Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. Results:In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I 2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Conclusion:Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. Neurology ® 2012;79:659-667 GLOSSARY CI ϭ confidence interval; GEO-PD ϭ Genetic Epidemiology of Parkinson's Disease; GWAS ϭ genome-wide association studies; HWE ϭ Hardy-Weinberg equilibrium; MALDI-TOF ϭ matrix-assisted laser desorption/ionization time-of-flight; MSA ϭ multiple system atrophy; OR ϭ odds ratio; PD ϭ Parkinson disease; SNP ϭ single nucleotide polymorphism.

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“…PD exists both as an idiopathic and a familial disorder [1]. So far, there are 18 genes known to be linked to PD, termed PARK genes [2,3] (table 1). The occurrence of LBs has been described for familial as well as sporadic forms of PD.…”

Section: Parkinson's Disease and Other Synucleinopathiesmentioning

confidence: 99%

α-Synuclein in Parkinson's Disease: Pathogenic Function and Translation into Animal Models

Eschbach¹,

Danzer²

2013

Neurodegener Dis

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Parkinson's disease is a common neurodegenerative disease characterised by the loss of dopaminergic neurons in the substantia nigra pars compacta and the formation of α-synuclein aggregates found in Lewy bodies throughout the brain. Several α-synuclein transgenic mouse models have been generated, as well as viral-mediated overexpression of wild-type and mutated α-synuclein to mimic the disease and to delineate the pathogenic pathway of α-synuclein-mediated toxicity and neurodegeneration. In this review, we will recapitulate what we have learned about the function of α-synuclein and α-synuclein-mediated toxicity through studies of transgenic animal models, inducible animal models and viral-based models.

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Replication of MAPT and SNCA, but not PARK16‐18, as susceptibility genes for Parkinson's disease

Abstract: Background-Recent genome-wide association studies of Parkinson's disease have nominated three new susceptibility loci (PARK16-18) and confirmed two known risk genes (MAPT and SNCA) in populations of European ancestry. We sought to replicate these findings.

Cited by 69 publications

References 24 publications

Association between PARK16 gene polymorphisms and susceptibility of Parkinson's disease in a Chinese population

Association between PARK16 gene polymorphisms and susceptibility of Parkinson's disease in a Chinese population

Large-scale replication and heterogeneity in Parkinson disease genetic loci

α-Synuclein in Parkinson's Disease: Pathogenic Function and Translation into Animal Models

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