Dataset Information

Independent and joint effects of the MAPT and SNCA genes in Parkinson disease.

ABSTRACT: OBJECTIVE:We studied the independent and joint effects of the genes encoding alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta-analysis of individual data from case-control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium. METHODS:Participants of Caucasian ancestry were genotyped for a total of 4 SNCA (rs2583988, rs181489, rs356219, rs11931074) and 2 MAPT (rs1052553, rs242557) single nucleotide polymorphism (SNPs). Individual and joint effects of SNCA and MAPT SNPs were investigated using fixed- and random-effects logistic regression models. Interactions were studied on both a multiplicative and an additive scale, and using a case-control and case-only approach. RESULTS:Fifteen GEO-PD sites contributed a total of 5,302 cases and 4,161 controls. All 4 SNCA SNPs and the MAPT H1-haplotype-defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For SNCA, the strongest associations were observed for SNPs located at the 3' end of the gene. There was no evidence of statistical interaction between any of the 4 SNCA SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale. INTERPRETATION:This study confirms the association between PD and both SNCA SNPs and the H1 MAPT haplotype. It shows, based on a variety of approaches, that the joint action of variants in these 2 loci is consistent with independent effects of the genes without additional interacting effects.

SUBMITTER: Elbaz A

PROVIDER: S-EPMC3082599 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Independent and joint effects of the MAPT and SNCA genes in Parkinson disease.

Elbaz Alexis A Ross Owen A OA Ioannidis John P A JP Soto-Ortolaza Alexandra I AI Moisan Frédéric F Aasly Jan J Annesi Grazia G Bozi Maria M Brighina Laura L Chartier-Harlin Marie-Christine MC Destée Alain A Ferrarese Carlo C Ferraris Alessandro A Gibson J Mark JM Gispert Suzana S Hadjigeorgiou Georgios M GM Jasinska-Myga Barbara B Klein Christine C Krüger Rejko R Lambert Jean-Charles JC Lohmann Katja K van de Loo Simone S Loriot Marie-Anne MA Lynch Timothy T Mellick George D GD Mutez Eugénie E Nilsson Christer C Opala Grzegorz G Puschmann Andreas A Quattrone Aldo A Sharma Manu M Silburn Peter A PA Stefanis Leonidas L Uitti Ryan J RJ Valente Enza Maria EM Vilariño-Güell Carles C Wirdefeldt Karin K Wszolek Zbigniew K ZK Xiromerisiou Georgia G Maraganore Demetrius M DM Farrer Matthew J MJ

Annals of neurology 20110309 5

<h4>Objective</h4>We studied the independent and joint effects of the genes encoding alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta-analysis of individual data from case-control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium.<h4>Methods</h4>Participants of Caucasian ancestry were genotyped for a total of 4 SNCA (rs2583988, rs181489, rs356219, rs11931074) and 2 MAPT (rs1052553, rs ...[more]

PMID: 21391235

Similar Datasets

Project description:ImportanceCognitive impairment is a common and disabling problem in Parkinson disease (PD) that is not well understood and is difficult to treat. Identification of genetic variants that influence the rate of cognitive decline or pattern of early cognitive deficits in PD might provide a clearer understanding of the etiopathogenesis of this important nonmotor feature.ObjectiveTo determine whether common variation in the APOE, MAPT, and SNCA genes is associated with cognitive performance in patients with PD.Design, setting, and participantsWe studied 1079 PD patients from 6 academic centers in the United States who underwent assessments of memory (Hopkins Verbal Learning Test-Revised [HVLT-R]), attention and executive function (Letter-Number Sequencing Test and Trail Making Test), language processing (semantic and phonemic verbal fluency tests), visuospatial skills (Benton Judgment of Line Orientation test), and global cognitive function (Montreal Cognitive Assessment). Participants underwent genotyping for the APOE ε2/ε3/ε4 alleles, MAPT H1/H2 haplotypes, and SNCA rs356219. We used linear regression to test for association between genotype and baseline cognitive performance with adjustment for age, sex, years of education, disease duration, and site. We used a Bonferroni correction to adjust for the 9 comparisons that were performed for each gene.Main outcomes and measuresNine variables derived from 7 psychometric tests.ResultsThe APOE ε4 allele was associated with lower performance on the HVLT-R Total Recall (P = 6.7 × 10(-6); corrected P [Pc] = 6.0 × 10(-5)), Delayed Recall (P = .001; Pc = .009), and Recognition Discrimination Index (P = .004; Pc = .04); a semantic verbal fluency test (P = .002; Pc = .02); the Letter-Number Sequencing Test (P = 1 × 10(-5); Pc = 9 × 10(-5)); and Trail Making Test B minus Trail Making Test A (P = .002; Pc = .02). In a subset of 645 patients without dementia, the APOE ε4 allele was associated with lower scores on the HVLT-R Total Recall (P = .005; Pc = .045) and the semantic verbal fluency (P = .005; Pc = .045) measures. Variants of MAPT and SNCA were not associated with scores on any tests.Conclusions and relevanceOur data indicate that the APOE ε4 allele is an important predictor of cognitive function in PD across multiple domains. Among PD patients without dementia, the APOE ε4 allele was only associated with lower performance on word list learning and semantic verbal fluency, a pattern more typical of the cognitive deficits seen in early Alzheimer disease than PD.

Dataset Information

Independent and joint effects of the MAPT and SNCA genes in Parkinson disease.

Publications

Independent and joint effects of the MAPT and SNCA genes in Parkinson disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets