Objective This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European‐ancestry subjects, and to increase the diversity in PD genome‐wide association (GWAS) data. Methods We genotyped and imputed 1,497 PD cases and controls recruited from nine clinical sites across South America. We performed a GWAS using logistic mixed models; variants with a p‐value <1 × 10−5 were tested in a replication cohort of 1,234 self‐reported Latino PD cases and 439,522 Latino controls from 23andMe, Inc. We also performed an admixture mapping analysis where local ancestry blocks were tested for association with PD status. Results One locus, SNCA, achieved genome‐wide significance (p‐value <5 × 10−8); rs356182 achieved genome‐wide significance in both the discovery and the replication cohorts (discovery, G allele: 1.58 OR, 95% CI 1.35–1.86, p‐value 2.48 × 10−8; 23andMe, G allele: 1.26 OR, 95% CI 1.16–1.37, p‐value 4.55 × 10−8). In our admixture mapping analysis, a locus on chromosome 14, containing the gene STXBP6, achieved significance in a joint test of ancestries and in the Native American single‐ancestry test (p‐value <5 × 10−5). A second locus on chromosome 6, containing the gene RPS6KA2, achieved significance in the African single‐ancestry test (p‐value <5 × 10−5). Interpretation This study demonstrated the importance of the SNCA locus for the etiology of PD in Latinos. By leveraging the demographic history of our cohort via admixture mapping, we identified two potential PD risk loci that merit further study. ANN NEUROL 2021;90:353–365
Background Human genetics research lacks diversity; over 80% of genome‐wide association studies have been conducted on individuals of European ancestry. In addition to limiting insights regarding disease mechanisms, disproportionate representation can create disparities preventing equitable implementation of personalized medicine. Objective This systematic review provides an overview of research involving Parkinson's disease (PD) genetics in underrepresented populations (URP) and sets a baseline to measure the future impact of current efforts in those populations. Methods We searched PubMed and EMBASE until October 2021 using search strings for “PD,” “genetics,” the main “URP,” and and the countries in Latin America, Caribbean, Africa, Asia, and Oceania (excluding Australia and New Zealand). Inclusion criteria were original studies, written in English, reporting genetic results on PD from non‐European populations. Two levels of independent reviewers identified and extracted information. Results We observed imbalances in PD genetic studies among URPs. Asian participants from Greater China were described in the majority of the articles published (57%), but other populations were less well studied; for example, Blacks were represented in just 4.0% of the publications. Also, although idiopathic PD was more studied than monogenic forms of the disease, most studies analyzed a limited number of genetic variants. We identified just nine studies using a genome‐wide approach published up to 2021, including URPs. Conclusion This review provides insight into the significant lack of population diversity in PD research highlighting the immediate need for better representation. The Global Parkinson's Genetics Program (GP2) and similar initiatives aim to impact research in URPs, and the early metrics presented here can be used to measure progress in the field of PD genetics in the future. © 2022 International Parkinson and Movement Disorder Society.
Neurophobia is a global issue known as a fear of Neurology and Neurosciences by medical students and physicians, and it may contribute to a reduced number of trained neurologists and a global mi PALAVRAS-CHAVE-Neurologia.-Educação.-Brasil. RESUMO A Neurofobia é um problema global conhecido como uma aversão à Neurologia e às
Hand Tremor and Inertial Measures using few features led to similar decision of the algorithms. Moreover, performance increased significantly according to the number of features used, reaching a plateau around 136. Finally, the results of this study suggested that kNN was the best algorithm to classify hand resting tremor in patients with PD.
BackgroundThe Montreal Cognitive Assessment (MoCA) is a short global cognitive scale, and some studies suggest it is useful for evaluating cognition in patients with Parkinson's disease (PD). However, its accuracy has been questioned in studies involving patients with low education.ObjectiveWe sought to assess whether some of the MoCA subtests contribute to the low accuracy of the test.MethodsWe performed a cross-sectional retrospective analysis of clinical data in a cohort of 71 patients with PD, most with less than 8 years of education. Patients were examined using the MDS-UPDRS, Hoehn and Yahr and the MoCA. The data were analyzed using mainly descriptive statistics.ResultsWe analyzed the data of 66 patients that were not demented according to the clinical evaluation and classified them using the proposed cut-off MoCA scores for diagnosis of MCI and dementia. Thirteen patients (19.7%) were classified as having normal cognition, 24 (36.3%) MCI and 29 (43.9%) dementia. Patients with dementia had longer disease duration (p=0.016) and lower education (p=0.0001). Total MoCA scores had a an almost normal distribution with a wide range of scores and only one maximum score. Performance on the MoCA was highly correlated with education (correlation coefficient=0.66, p=0.0001). At least five of the 10 MoCA subtests showed significant floor effects.ConclusionWe believe that some of the MoCA subtests may be too difficult to be completed by PD patients with low educational level, thus contributing to the test's poor diagnostic accuracy.
Parkinson’s disease (PD) is the second-most common neurodegenerative disease, and its pathophysiology is associated with alpha-synuclein accumulation, oxidative stress, mitochondrial dysfunction, and neuroinflammation. MicroRNAs are small non-coding RNAs that regulate gene expression, and many previous studies have described their dysregulation in plasma, CSF, and in the brain of patients with PD. In this study, we aimed to provide a regulatory network analysis on differentially expressed miRNAs in the brain of patients with PD. Based on our systematic review with a focus on the substantia nigra and the putamen, we found 99 differentially expressed miRNAs in brain samples from patients with PD, which regulate 135 target genes. Five genes associated with neuronal survival (BCL2, CCND1, FOXO3, MYC, and SIRT1) were modulated by dysregulated miRNAs found in the substantia nigra and the putamen of patients with PD. The functional enrichment analysis found FoxO and PI3K-AKT signaling as pathways related to PD. In conclusion, our comprehensive analysis of brain-related miRNA–mRNA regulatory networks in PD showed that mechanisms involving neuronal survival signaling, such as cell cycle control and regulation of autophagy/apoptosis, may be crucial for the neurodegeneration of PD, being a promising way for novel disease-modifying therapies.
To date, over 90 Parkinson’s disease (PD) risk variants have been reported from genome-wide association studies (GWAS). However, these GWAS efforts have been limited to individuals of European and East Asian ancestry. We performed the first GWAS of Latino PD patients from South America, comparing 807 cases against 690 controls followed by association testing of suggestive loci in a replication cohort of 1,234 cases and 439,522 controls. We demonstrated that SNCA plays a significant role in PD etiology in a Latino cohort and identified a suggestive locus near NRROS on chromosome 3 that appeared to be driven by Peruvian subjects. We also characterized the overlap of PD genetic architecture between Europeans and Latinos with a replication of significant variants identified by Nalls et al. in their 2019 GWAS1, finding 80% concordance in direction of effect. We then leveraged the population history of Latinos via admixture mapping, identifying a significant locus on chromosome 14 in a joint test of ancestries, driven by the Native American ancestral background, and a significant locus on chromosome 6 in our test of African ancestry, containing the genes STXBP6 and RPS6KA2, respectively. Ultimately, our work reflects the most comprehensive characterization of PD genetic architecture in Latinos to date.
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