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Updated: Jul 12, 2026

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Published on: August 20, 2019
LRRK2 in Focus: A Global Browser Linking Genetic Diversity to Functional Effects
Spencer M Grant1,2, Vesna van Midden3, Elias Fernandez-Toledo4
1Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
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.
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