Introduction: Parkinson's Disease (PD) is a progressive neurodegenerative disorder affecting 2-3% of the global population over 65 years [1]. Its prevalence is increasing worldwide in both developed and developing countries. Previous research has been predominantly focused on populations of European descent, limiting the applicability of findings to global populations [2,3]. PD exhibits a complex genetic etiology encompassing both idiopathic and familial forms, with familial cases believed to be monogenic and accounting for 5-10% of all instances [4]. The Australian Parkinson’s Genetics Study (APGS), Monogenic Parkinson’s Disease Australia (MonoPDAus), and the MEX-PD Project, under the Global Parkinson’s Genetics Program (GP2), aim to elucidate the genetic underpinnings of PD across diverse populations.
Objectives: This study utilises data from APGS/MonoPDAus and MEX-PD to (i) identify patients with suspected familial PD, based on early age of onset and/or family history; (ii) identify novel pathogenic variants and genes associated with monogenic PD, particularly among underrepresented groups; (iii) establish genotype-phenotype correlations for PD genes and their clinical manifestations; (iv) apply a consistent analysis workflow across Australian and Mexican cohorts.
Methods: We will prioritise 1,000 APGS participants with positive family history and/or early-onset PD for whole-genome sequencing, with a focus on diverse Australian population groups. Similarly, 68 participants from MEX-PD, identified as potential monogenic PD cases, will also undergo this process. For both groups, neurologists and movement disorder specialists will recontact and assess patients to gather phenotypic data and biological samples. The clinical and genetic data will undergo quality control, and analysis using bioinformatic pipelines to identify, annotate, prioritise, interpret, curate, and validate known and novel pathogenic variants, as well as candidate genes associated with monogenic PD.