Genomic determinants of motor and cognitive outcomes in Parkinson's disease.
Ontology highlight
ABSTRACT: Background
Little is known regarding genetic factors associated with motor or cognitive outcomes in Parkinson's disease (PD).Objective
To identify common genetic variants associated with motor and cognitive outcomes in PD.Methods
The sample consisted of 443 PD cases included in the first genome-wide association study (GWAS) of PD. Methods included telephone interview assessments of motor and cognitive outcomes, a median 9 years following the initial clinical assessments. Analyses included Cox proportional hazard models to study the association of 198,345 single nucleotide polymorphisms (SNPs) with survival free of Hoehn and Yahr stage ≥ 4 (motor outcome), and either TICS-M ≤ 27 or AD-8 ≥ 2 (cognitive outcomes).Results
The SNP rs10958605 in the C8orf4 gene had the smallest p value in analyses of the motor outcome (HR = 1.81; 95% CI = 1.42-2.31; p = 1.51 × 10(-6)). The SNP rs6482992 in the CLRN3 gene had the smallest p value in analyses of the cognitive outcome (HR = 2.03, 95% CI 1.47-2.79, p = 4.08 × 10(-6)). However, no SNP associations were significant after Bonferroni correction. The C8orf4 gene had small p values for both motor and cognitive outcomes, highlighting inflammation as a possible pathogenesis mechanism for progression in PD.Conclusions
This study suggests that common variants in several genes may be associated with motor and cognitive outcomes in PD, with biological plausibility.
SUBMITTER: Chung SJ
PROVIDER: S-EPMC3606821 | biostudies-literature | 2012 Aug
REPOSITORIES: biostudies-literature
Publications
Genomic determinants of motor and cognitive outcomes in Parkinson's disease.
Chung Sun Ju SJ Armasu Sebastian M SM Biernacka Joanna M JM Anderson Kari J KJ Lesnick Timothy G TG Rider David N DN Cunningham Julie M JM Eric Ahlskog J J Frigerio Roberta R Maraganore Demetrius M DM
Parkinsonism & related disorders 20120530 7
<h4>Background</h4>Little is known regarding genetic factors associated with motor or cognitive outcomes in Parkinson's disease (PD).<h4>Objective</h4>To identify common genetic variants associated with motor and cognitive outcomes in PD.<h4>Methods</h4>The sample consisted of 443 PD cases included in the first genome-wide association study (GWAS) of PD. Methods included telephone interview assessments of motor and cognitive outcomes, a median 9 years following the initial clinical assessments. ...[more]
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Project description:Background: Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by a clinical symptomatology involving both motor and non-motor symptoms. Motor complications associated with long-term dopaminergic treatment include motor fluctuations and levodopa-induced dyskinesia (LID), which may have a major impact on the quality of life. The clinical features and onset time of motor complications in the disease course are heterogeneous, and the etiology remains unknown. Objective: We aimed to identify genomic variants associated with the development of motor fluctuations and LID at 5 years after the onset of PD. Methods: Genomic data were obtained using Affymetrix Axiom KORV1.1 array, including an imputation genome-wide association study (GWAS) grid and other GWAS loci; functional variants of the non-synonymous exome; pharmacogenetic variants; variants in genes involved in absorption, distribution, metabolism, and excretion of drugs; and expression quantitative trait loci in 741 patients with PD. Results: FAM129B single-nucleotide polymorphism (SNP) rs10760490 was nominally associated with the occurrence of motor fluctuations at 5 years after the onset of PD [odds ratio (OR) = 2.9, 95% confidence interval (CI) = 1.8-4.8, P = 6.5 × 10-6]. GALNT14 SNP rs144125291 was significantly associated with the occurrence of LID (OR = 5.5, 95% CI = 2.9-10.3, P = 7.88 × 10-9) and was still significant after Bonferroni correction. Several other genetic variants were associated with the occurrence of motor fluctuations or LID, but the associations were not significant after Bonferroni correction. Conclusion: This study identified new loci associated with the occurrence of motor fluctuations and LID at 5 years after the onset of PD. However, further studies are needed to confirm our findings.
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