We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Hierarchical Data-Driven Analysis of Clinical Symptoms Among Patients With Parkinson's Disease.
- Authors
Kozlovski, Tal; Mitelpunkt, Alexis; Thaler, Avner; Gurevich, Tanya; Orr-Urtreger, Avi; Gana-Weisz, Mali; Shachar, Netta; Galili, Tal; Marcus-Kalish, Mira; Bressman, Susan; Marder, Karen; Giladi, Nir; Benjamini, Yoav; Mirelman, Anat
- Abstract
Mutations in the LRRK2 and GBA genes are the most common inherited causes of Parkinson's disease (PD). Studies exploring phenotypic differences based on genetic status used hypothesis-driven data-gathering and statistical-analyses focusing on specific symptoms, which may influence the validity of the results. We aimed to explore phenotypic expression in idiopathic PD (iPD) patients, G2019S-LRRK2-PD, and GBA-PD using a data-driven approach, allowing screening of large numbers of features while controlling selection bias. Data was collected from 1525 Ashkenazi Jews diagnosed with PD from the Tel-Aviv Medical center; 161 G2019S-LRRK2-PD, 222 GBA-PD, and 1142 iPD (no G2019S-LRRK2 or any of the 7 AJ GBA mutations tested). Data included 771 measures: demographics, cognitive, physical and neurological functions, performance-based measures, and non-motor symptoms. The association of the genotypes with each of the measures was tested while accounting for age at motor symptoms onset, gender, and disease duration; p -values were reported and corrected in a hierarchical approach for an average over the selected measures false discovery rate control, resulting in 32 measures. GBA-PD presented with more severe symptoms expression while LRRK2-PD had more benign symptoms compared to iPD. GBA-PD presented greater cognitive and autonomic involvement, more frequent hyposmia and REM sleep behavior symptoms while these were less frequent among LRRK2-PD compared to iPD. Using a data-driven analytical approach strengthens earlier studies and extends them to portray a possible unique disease phenotype based on genotype among AJ PD. Such findings could help direct a more personalized therapeutic approach.
- Subjects
PARKINSON'S disease treatment; CLINICAL trials; GENOTYPES; COGNITIVE ability; INFERENCE (Logic)
- Publication
Frontiers in Neurology, 2019, pN.PAG
- ISSN
1664-2295
- Publication type
Article
- DOI
10.3389/fneur.2019.00531