Rare but Relevant: Assessing Variants in Dystonia-linked Genes in Parkinson's Disease.

Background: Dystonia and Parkinson's disease (PD) show clinical and genetic overlap, but the relevance of dystonia gene variants in PD remains unclear.

Objective: To assess the frequency of dystonia-linked pathogenic variants in PD.

Methods: We screened sequencing data from 15,738 individuals (7,851 PD, 4,287 atypical parkinsonism, and 3,600 unaffected) from GP2 and AMP-PD for variants in genes linked to isolated dystonia, dystonia-parkinsonism, and myoclonus-dystonia.

The Global Landscape of Genetic Variation in Parkinson's disease: Multi-Ancestry Insights into Established Disease Genes and their Translational Relevance.

Background: The genetic architecture of Parkinson's disease (PD) varies considerably across ancestries, yet most genetic studies have focused on individuals of European descent, limiting our insights into the genetic architecture of PD at a global scale.

Methods: We conducted a large-scale, multi-ancestry investigation of causal and risk variants in PD-related genes. Using genetic datasets from the Global Parkinson's Genetics Program, we analyzed sequencing and genotyping data from 69,881 individuals, including 41,139 affected and 28,742 unaffected, from eleven different ancestries, including ~30% of individuals from non-European ancestries.

Parkinson's families project: a UK-wide study of early onset and familial Parkinson's disease.

The Parkinson's Families Project is a UK-wide study aimed at identifying genetic variation associated with familial and early-onset Parkinson's disease (PD). We recruited individuals with a clinical diagnosis of PD and age at motor symptom onset ≤45 years and/or a family history of PD in up to third-degree relatives. Where possible, we also recruited affected and unaffected relatives.

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2).

The Global Parkinson's 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.