Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data.
ABSTRACT Several genes underlying rare monogenic forms of Parkinson's disease have been identified over the past decade. Despite evidence for a role for genetics in sporadic Parkinson's disease, few common genetic variants have been unequivocally linked to this disorder. We sought to identify any common genetic variability exerting a large effect in risk for Parkinson's disease in a population cohort and to produce publicly available genome-wide genotype data that can be openly mined by interested researchers and readily augmented by genotyping of additional repository subjects.
We did genome-wide, single-nucleotide-polymorphism (SNP) genotyping of publicly available samples from a cohort of Parkinson's disease patients (n=267) and neurologically normal controls (n=270). More than 408,000 unique SNPs were used from the Illumina Infinium I and HumanHap300 assays.
We have produced around 220 million genotypes in 537 participants. This raw genotype data has been and as such is the first publicly accessible high-density SNP data outside of the International HapMap Project. We also provide here the results of genotype and allele association tests.
We generated publicly available genotype data for Parkinson's disease patients and controls so that these data can be mined and augmented by other researchers to identify common genetic variability that results in minor and moderate risk for disease.
- SourceAvailable from: de.arxiv.org[Show abstract] [Hide abstract]
ABSTRACT: We demonstrate and analyze an aggregation method for sparse logistic regression in high-dimensional settings. This approach linearly combines the estimators from various logistic models with different sparsity patterns and can balance the predictive ability and model interpretability. We also study the Kullback-Leibler risk of the aggregation estimator and show that it is comparable to the risk of the best estimator based on a single logistic regression, chosen by an oracle. Numerical performance of the estimator is also investigated using both simulated and real data.10/2014;
- [Show abstract] [Hide abstract]
ABSTRACT: Parkinson's disease (PD) can be divided in familial (Mendelian) and sporadic forms. A number of causal genes have been discovered for the Mendelian form, which constitutes 10-20% of the total cases. Genome-wide association studies (GWASs) have successfully uncovered a number of susceptibility loci for sporadic cases but those only explain a small fraction (6-7%) of PD heritability. It has been observed that some genes that confer susceptibility to PD through common risk variants also contain rare causing mutations for the Mendelian forms of the disease. These results suggest a possible functional link between Mendelian and sporadic PD and led us to investigate the role that rare and low-frequency variants could have on the sporadic form. Through a targeting approach, we have resequenced at 49X coverage the exons and regulatory regions of 38 genes (including Mendelian and susceptibility PD genes) in 249 sporadic PD patients and 145 unrelated controls of European origin. Unlike susceptibility genes, Mendelian genes show a clear general enrichment of rare functional variants in PD cases, observed directly as well as with Tajima's D statistic and several collapsing methods. Our findings suggest that rare variation on PD Mendelian genes may have a role in the sporadic forms of the disease. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: email@example.com.Human Molecular Genetics 12/2014; · 6.68 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: It has been reported that single nucleotide polymorphisms (SNPs) of Alpha-synuclein (SNCA) are associated with Parkinson's disease (PD). Some researchers have attempted to validate this finding in various ethnic populations. The results of studies concerning SNCA polymorphisms and PD susceptibility remain conflicting. To evaluate the association between these SNPs and PD, the authors conducted a series of meta-analyses using a predefined protocol. Databases including PubMed, MEDLINE and PD gene were searched to identify relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. All analyses were calculated using STATA11.0. A total of 19 studies on the SNPS rs181489, rs356186, rs356219, rs894278, rs2583988, rs2619363, rs2619364, rs2737029, rs10005233 and rs11931074 were included. This meta-analysis showed that eight out of these 10 candidate SNPs may be associated with PD risk. Significant association was found between PD and the following SNPs: rs181489, rs356186, rs356219, rs894278 rs2583988, rs2619364, rs10005233 and rs11931074. Among these SNPs, rs356186 was found to be the only SNP that may play a protective role in Parkinson's disease. These results suggest that the SNCA gene may be associated with PD. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 02/2015; 168(2). · 3.27 Impact Factor