Hierarchical Data-Driven Analysis of Clinical Symptoms Among Patients With Parkinson's Disease

• Published in: Frontiers in neurology Vol. 10; p. 531
• Main 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 21-05-2019
• Subjects: G2019S-LRRK2; GBA; hierarchical testing; Neurology; Parkinson's disease; selective inference; hierarchical testing; G2019S-LRRK2; Parkinson's disease; selective inference; GBA
• ISSN: 1664-2295; 1664-2295
• DOI: 10.3389/fneur.2019.00531

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;
-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.