• Home
  • /
  • < Back To News
  • /
  • Genomewide association study of Parkinson's disease clinical biomarkers in 12 longitudinal patients' cohorts

Genomewide association study of Parkinson's disease clinical biomarkers in 12 longitudinal patients' cohorts

By:
Hirotaka Iwaki et. al PDBP authors: Clemens Scherzer, Andy Singleton & Mike Nalls
Summary of analytical processes
Credit: https://onlinelibrary.wiley.com/doi/full/10.1002/m...

Background:

Several reports have identified different patterns of Parkinson's disease progression in individuals carrying missense variants in GBA or LRRK2 genes. The overall contribution of genetic factors to the severity and progression of Parkinson's disease, however, has not been well studied.

Objectives:

To test the association between genetic variants and the clinical features of Parkinson's disease on a genomewide scale.

Methods:

We accumulated individual data from 12 longitudinal cohorts in a total of 4093 patients with 22,307 observations for a median of 3.81 years. Genomewide associations were evaluated for 25 cross‐sectional and longitudinal phenotypes. Specific variants of interest, including 90 recently identified disease‐risk variants, were also investigated post hoc for candidate associations with these phenotypes.

Results:

Two variants were genomewide significant. Rs382940(T>A), within the intron of SLC44A1, was associated with reaching Hoehn and Yahr stage 3 or higher faster (hazard ratio 2.04 [1.58–2.62]; P value = 3.46E‐8). Rs61863020(G>A), an intergenic variant and expression quantitative trait loci for α‐2A adrenergic receptor, was associated with a lower prevalence of insomnia at baseline (odds ratio 0.63 [0.52–0.75]; P value = 4.74E‐8). In the targeted analysis, we found 9 associations between known Parkinson's risk variants and more severe motor/cognitive symptoms. Also, we replicated previous reports of GBA coding variants (rs2230288: p.E365K; rs75548401: p.T408M) being associated with greater motor and cognitive decline over time, and an APOE E4 tagging variant (rs429358) being associated with greater cognitive deficits in patients.

Conclusions:

We identified novel genetic factors associated with heterogeneity of Parkinson's disease. The results can be used for validation or hypothesis tests regarding Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society

Full Article:

https://onlinelibrary.wiley.com/doi/full/10.1002/mds.27845#mds27845-fig-0001

PMID: 31505070

DOI: 10.1002/mds.27845

 

Recent Articles

Single molecule array measures of LRRK2 kinase activity in serum link Parkinson’s disease severity to peripheral inflammation
Lewy body pathology modifies risk factors for cerebral amyloid angiopathy when comorbid with Alzheimer's disease pathology
Plasma biomarkers of Alzheimer's disease in the continuum of dementia with Lewy bodies
Altered structural and functional connectivity in Posterior Cortical Atrophy and Dementia with Lewy bodies
Grey matter networks in women and men with dementia with Lewy bodies
Influences of amyloid-β and tau on white matter neurite alterations in dementia with Lewy bodies
Sex differences in brain atrophy in dementia with Lewy bodies
Role of GBA variants in Lewy body disease neuropathology
ATN cerebrospinal fluid biomarkers in dementia with Lewy bodies: Initial results from the United States Dementia with Lewy Bodies Consortium
Genetic risk variants in New Yorkers of Puerto Rican and Dominican Republic heritage with Parkinson’s disease
Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease
Seed amplification assay results illustrate discrepancy in Parkinson’s disease clinical diagnostic accuracy and error rates
β-Amyloid Load on PET Along the Continuum of Dementia With Lewy Bodies
A Preliminary Comparison of the Methylome and Transcriptome from the Prefrontal Cortex Across Alzheimer’s Disease and Lewy Body Dementia
Genome-Wide Analysis of Structural Variants in Parkinson Disease
Cross-sectional Associations of β-Amyloid, Tau, and Cerebrovascular Biomarkers With Neurodegeneration in Probable Dementia With Lewy Bodies
Mass spectrometry-based proteomics analysis of human substantia nigra from Parkinson's disease patients identifies multiple pathways potentially involved in the disease
Mass spectrometry-based proteomics analysis of human globus pallidus from progressive supranuclear palsy patients discovers multiple disease pathways
APDM gait and balance measures fail to predict symptom progression rate in Parkinson's disease
Mitochondrial haplogroups and cognitive progression in Parkinson’s disease
Parkinson-causing mutations in LRRK2 impair the physiological tetramerization of endogenous α-synuclein in human neurons
GRN Mutations Are Associated with Lewy Body Dementia
Differences in Sex-Specific Frequency of Glucocerebrosidase Variant Carriers and Familial Parkinsonism
Mitochondrial genomic variation in dementia with Lewy bodies: association with disease risk and neuropathological measures
Association of Olfactory Performance With Motor Decline and Age at Onset in People With Parkinson Disease and the LRRK2 G2019S Variant
Dynamics of nigral iron accumulation in Parkinson’s disease: from diagnosis to late stage
Elevated Urinary Rab10 Phosphorylation in Idiopathic Parkinson Disease
Advanced diffusion imaging to track progression in Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy
Multi-modality machine learning predicting Parkinson’s disease
High-Sensitivity Single Molecule Array Assays for Pathological Isoforms in Parkinson’s Disease
Parkinson Disease and SubthalamicNucleus Deep Brain Stimulation:Cognitive Effects inGBAMutationCarriers
Longitudinal risk factors for developing depressive symptoms in Parkinson's disease
Discovery of Parkinson's disease states and disease progression modelling: a longitudinal data study using machine learning
Lateralization of Motor Signs Affects Symptom Progression in Parkinson Disease
Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson’s disease
Association of Dual LRRK2 G2019S and GBA Variations With Parkinson Disease Progression
Probable REM Sleep Behavior Disorder Is a Risk Factor for Symptom Progression in Parkinson Disease
Predicting Parkinson's disease trajectory using clinical and neuroimaging baseline measures
Oral Levodopa Formulation Does Not Affect Progression of Parkinson Disease
Differential blood DNA methylation across Lewy body dementias
Isradipine plasma pharmacokinetics and exposure–response in early Parkinson’s disease
β-Amyloid PET and 123I-FP-CIT SPECT in Mild Cognitive Impairment at Risk for Lewy Body Dementia
View all news