Year: 2026
Type: preprint
Abstract: Background LRRK2 variants are major contributors to Parkinson’s disease (PD). Many pathogenic variants increase kinase activity, underscoring the value of functional assays in nominating therapeutic targets and kinase inhibitors as potential disease-modifying therapies. Objective To develop an interactive resource that provides functional context and ancestry-specific variant frequencies. Methods Genotyping and short-read sequencing data were analyzed for 101,678 individuals (61,709 PD, 39,969 controls) from the Global Parkinson’s Genetics Program (GP2) and integrated with clinical and in-vitro biochemical kinase activity information. Results The LRRK2 Browser ( http://gp2.org/lrrk2browser ) displays ancestry-specific genetic data for 19,596 LRRK2 variants (968 exonic, 14 disease-associated) across 11 populations, and functional data for 171 variants. Clinical annotations include age, age at onset, and family history of PD. Discussion The publicly available LRRK2 Browser represents an open-access, multi-ancestry resource to support LRRK2 variant interpretation. It aims to enhance the translational potential of genetic and functional data for precision medicine and the implementation of gene-targeted therapies in diverse populations.
Source: medRxiv
Institutions: National Institutes of Health, University of Cambridge, National Institute of Neurological Disorders and Stroke, National Institute on Aging, Ljubljana University Medical Centre, University of Concepción, University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit, UCL Queen Square Institute of Neurology, University College London, Coalition for Aligning Science, University of Lübeck
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7167367663