| Literature DB >> 33781610 |
Yuri L Sosero1, Eric Yu1, Lynne Krohn1, Uladzislau Rudakou1, Kheireddin Mufti1, Jennifer A Ruskey2, Farnaz Asayesh2, Sandra B Laurent3, Dan Spiegelman4, Stanley Fahn5, Cheryl Waters5, S Pablo Sardi6, Sara Bandres-Ciga7, Roy N Alcalay8, Ziv Gan-Or9, Konstantin Senkevich10.
Abstract
The LRRK2 p.G2019S Parkinson's disease (PD) variant is associated with elevated glucocerebrosidase (GCase) activity in peripheral blood. We aimed to evaluate the association of other LRRK2 variants with PD and its association with GCase activity. LRRK2 and GBA were fully sequenced in 1123 PD patients and 576 controls from the Columbia and PPMI cohorts, in which GCase activity was measured in dried blood spots by liquid chromatography-tandem mass spectrometry. LRRK2 p.M1646T was associated with increased GCase activity in the Columbia University cohort (β = 1.58, p = 0.0003), and increased but not significantly in the PPMI cohort (β = 0.29, p = 0.58). p.M1646T was associated with PD (odds ratio = 1.18, 95% confidence interval = 1.09-1.28, p = 7.33E-05) in 56,306 PD patients and proxy-cases, and 1.4 million controls. Our results suggest that the p.M1646T variant is associated with risk of PD with a small effect and with increased GCase activity in peripheral blood.Entities:
Keywords: GBA; Glucocerebrosidase; LRRK2; Parkinson's disease
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Year: 2021 PMID： 33781610 PMCID： PMC8178224 DOI： 10.1016/j.neurobiolaging.2021.02.018
Source DB: PubMed Journal: Neurobiol Aging ISSN： 0197-4580 Impact factor: 5.133