9 research outputs found
Author Correction: Elucidating causative gene variants in hereditary Parkinsonâs disease in the Global Parkinsonâs Genetics Program (GP2)
Correction to: npj Parkinsonâs Disease, published online 27 June 2023 In this article the Global Parkinsonâs Genetics Program (GP2) members names and affiliations were missing in the main author list of the Original article which are listed in the below
Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort
Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotypeâphenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Defining the causes of sporadic Parkinsonâs disease in the global Parkinsonâs genetics program (GP2)
\ua9 2023, Springer Nature Limited. The Global Parkinsonâs Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia
Multi-ancestry genome-wide association meta-analysis of Parkinsonâs disease
\ua9 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. Although over 90 independent risk variants have been identified for Parkinsonâs disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinsonâs disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations
Defining the causes of sporadic Parkinsonâs disease in the global Parkinsonâs genetics program (GP2)
The Global Parkinsonâs Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia
Author Correction: Elucidating causative gene variants in hereditary Parkinsonâs disease in the Global Parkinsonâs Genetics Program (GP2)
Correction to: s41531-023-00526-9 npj Parkinsonâs Disease, published online 27 June 2023 In this article the Global Parkinsonâs Genetics Program (GP2) members names and affiliations were missing in the main author list of the Original article which are listed in the below
Validation of conversion between miniâmental state examination and montreal cognitive assessment
Introduction: Harmonizing data across cohorts is important for validating findings or combining data in metaâanalyses. We replicate and validate a previous conversion of MoCA to MMSE in PD. Methods: We used five studies with 1,161 PD individuals and 2,091 observations measured with both the MoCA and MMSE. We compared a previously published conversion table using equipercentile equating with logâlinear smoothing to our internally derived scores. Results: Both conversions found good agreement within and across the studies when comparing true and converted MMSE (mean difference: 0.05; standard deviation: 1.84; median difference: 0; interquartile range: â1 to 1, using internal conversion). Conclusions: These results show that one can get a reliable and valid conversion between two commonly used measures of cognition in PD studies. These approaches need to be applied to other scales and domains to enable largeâscale collaborative analyses across multiple PD cohorts. © 2016 International Parkinson and Movement Disorder Society </p
Author Correction: Elucidating causative gene variants in hereditary Parkinsonâs disease in the Global Parkinsonâs Genetics Program (GP2) (npj Parkinson\u27s Disease, (2023), 9, 1, (100), 10.1038/s41531-023-00526-9)
\ua9 2023, Springer Nature Limited.Correction to: npj Parkinsonâs Disease, published online 27 June 2023 In this article the Global Parkinsonâs Genetics Program (GP2) members names and affiliations were missing in the main author list of the Original article which are listed in the below