| Title: | LRRK2 rare-variant per-domain genetic burden in Parkinson's Disease: association confined to the kinase domain |
| Journal: | npj Parkinson's Disease |
| Published: | 29 Apr 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40301370/ |
| DOI: | https://doi.org/10.1038/s41531-025-00934-z |
| URL: | https://www.nature.com/articles/s41531-025-00934-z.pdf |
Publication 15728
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Abstract
LRRK2 variants are key genetic risk factors for Parkinson's Disease (PD). We conducted a per-domain rare coding variant burden analysis, including 8,888 PD cases and 69,412 controls. In meta-analysis, the Kinase domain was strongly associated with PD (Exonic: PFDR = 1.61 × 10−22, Non-synonymous: PFDR = 1.54 × 10−23, CADD > 20: PFDR = 3.09 × 10−24). Excluding the p.G2019S variant nullified this effect. Nominal associations were found in the ANK and Roc-COR domains, with potentially protective variants, p.R793M and p.Q1353K.</p>
21 Authors
- Sitki Cem Parlar
- Konstantin Senkevich
- Eric Yu
- Jennifer A. Ruskey
- Jamil Ahmad
- Farnaz Asayesh
- Dan Spiegelman
- Cheryl Waters
- Oury Monchi
- Yves Dauvilliers
- Nicolas Dupré
- Lior Greenbaum
- Sharon Hassin-Baer
- Irina Miliukhina
- Alla Timofeeva
- Anton Emelyanov
- Sofya Pchelina
- Roy N. Alcalay
- Edward A. Fon
- Jean-François Trempe
- Ziv Gan-Or
1 Application
| Application ID | Title |
|---|---|
| 45551 | Mechanistic modelling of neurodevelopment, neuroplasticity, and neurodegeneration |
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