Dataset Information

Parkinson's disease susceptibility variants and severity of Lewy body pathology.

ABSTRACT: INTRODUCTION:Meta-analyses of genome-wide association studies (GWAS) have established common genetic risk factors for clinical Parkinson's disease (PD); however, associations between these risk factors and quantitative neuropathologic markers of disease severity have not been well-studied. This study evaluated associations of nominated variants from the most recent PD GWAS meta-analysis with Lewy body disease (LBD) subtype (brainstem, transitional, or diffuse) and pathologic burden of LB pathology as measured by LB counts in five cortical regions in a series of LBD cases. METHODS:547 autopsy-confirmed cases of LBD were included and genotyped for 29 different GWAS-nominated PD risk variants. LB counts were measured in middle frontal (MF), superior temporal (ST), inferior parietal (IP), cingulate (CG), and parahippocampal (PH) gyri. RESULTS:None of the variants examined were significantly associated with LB counts in any brain region or with LBD subtype after correcting for multiple testing. Nominally significant (P < 0.05) associations with LB counts where the direction of association was in agreement with that observed in the PD GWAS meta-analysis were observed for variants in BCKDK/STX1B (MF, ST, IP) and SNCA (ST). Additionally, MIR4697 and BCKDK/STX1B variants were nominally associated with LBD subtype. CONCLUSION:The lack of a significant association between PD GWAS variants and severity of LB pathology is consistent with the generally subtle association odds ratios that have been observed in disease-risk analysis. These results also suggest that genetic factors other than the susceptibility loci may determine quantitative neuropathologic outcomes in patients with LBD.

SUBMITTER: Heckman MG

PROVIDER: S-EPMC5716921 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Parkinson's disease susceptibility variants and severity of Lewy body pathology.

Heckman Michael G MG Kasanuki Koji K Diehl Nancy N NN Koga Shunsuke S Soto Alexandra A Murray Melissa E ME Dickson Dennis W DW Ross Owen A OA

Parkinsonism & related disorders 20170911

<h4>Introduction</h4>Meta-analyses of genome-wide association studies (GWAS) have established common genetic risk factors for clinical Parkinson's disease (PD); however, associations between these risk factors and quantitative neuropathologic markers of disease severity have not been well-studied. This study evaluated associations of nominated variants from the most recent PD GWAS meta-analysis with Lewy body disease (LBD) subtype (brainstem, transitional, or diffuse) and pathologic burden of LB ...[more]

PMID: 28917824

Similar Datasets

Project description:BackgroundParkinson's disease (PD) is a condition that affects movement and is usually seen in those over the age of 50. It is caused by the death of dopaminergic neurons, particularly in the substantia nigra. PD has shifted from being perceived as an uncommon condition to a significant neurological illness, mostly due to the increasing number of elderly individuals and the impact of environmental factors. Parkinson's plus syndromes, such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and vascular Parkinsonism (VaP), provide difficulties in distinguishing them clinically from PD since they have similar characteristics.MethodologyA thorough examination was performed utilizing the PubMed, Medline, Scopus, and Web of Science databases. The search utilized specific keywords like "Parkinson's disease," "Parkinson's plus syndrome," "Lewy body dementia," "Alzheimer's dementia," "progressive supranuclear palsy," and "multiple system atrophy." The selection criteria were aimed at English-language literature, with a particular focus on examining the connection between PD and associated disorders or dementias.Results and discussionParkinson's plus syndromes, such as PSP, MSA, CBD, and VaP, exhibit unique clinical characteristics, imaging results, and diverse reactions to levodopa. This makes it difficult to distinguish them from PD. LBD is characterized by Lewy bodies containing α-synuclein, which leads to both motor and cognitive deficits. PD and Alzheimer's disease (AD) exhibit a complex interaction, including common pathogenic processes, genetic predispositions, and clinical characteristics of dementia.ConclusionThe interrelatedness of PD, Parkinson's plus syndromes, LBD, and AD highlights the significance of comprehending shared disease-causing processes. Aberrant protein clumping, impaired functioning of mitochondria, increased oxidative stress, and inflammation in the brain are common factors which can be addressed for specific treatments. More research is essential for understanding complicated connections and developing effective therapies for these sophisticated neurological illnesses.

Dataset Information

Parkinson's disease susceptibility variants and severity of Lewy body pathology.

Publications

Parkinson's disease susceptibility variants and severity of Lewy body pathology.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets