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Updated: Jul 12, 2026
06:41
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
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.
Medrxiv : the Preprint Server for Health Sciences
|July 10, 2026
Summary
The LRRK2 Browser offers a new resource for Parkinson's disease (PD) research, detailing genetic variants and their functional impact across diverse populations to advance precision medicine.
Area of Science:
- Genetics
- Neuroscience
- Biochemistry
Background:
- Pathogenic Leucine-rich repeat kinase 2 (LRRK2) variants are significant genetic contributors to Parkinson's disease (PD).
- Many disease-associated LRRK2 variants elevate kinase activity, highlighting the therapeutic potential of kinase inhibitors and the importance of functional assays.
Purpose of the Study:
- To create an interactive, open-access resource for Parkinson's disease research.
- To provide functional context and ancestry-specific variant frequencies for LRRK2.
Main Methods:
- Analysis of genotyping and short-read sequencing data from 101,678 individuals (61,709 PD patients, 39,969 controls) within the Global Parkinson's Genetics Program (GP2).
- Integration of clinical data and in-vitro biochemical kinase activity information for LRRK2 variants.
Main Results:
- The LRRK2 Browser (http://gp2.org/lrrk2browser) now hosts genetic data for 19,596 LRRK2 variants across 11 populations, including functional data for 171 variants.
- The resource includes clinical annotations such as age, age at onset, and family history of PD, alongside ancestry-specific variant frequencies for 968 exonic and 14 disease-associated variants.
Conclusions:
- The LRRK2 Browser serves as a valuable, publicly accessible, multi-ancestry platform for interpreting LRRK2 variants.
- This resource aims to accelerate the translation of genetic and functional insights into precision medicine and targeted therapies for diverse Parkinson's disease populations.
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