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TitleVariants in the Niemann-Pick type C gene NPC1 are not associated with Parkinson's disease.
Publication TypeJournal Article
Year of Publication2020
AuthorsBencheikh, Bouchra Ouled Amar, Konstantin Senkevich, Uladzislau Rudakou, Eric Yu, Kheireddin Mufti, Jennifer A. Ruskey, Farnaz Asayesh, Sandra B. Laurent, Dan Spiegelman, Stanley Fahn, Cheryl Waters, Oury Monchi, Yves Dauvilliers, Alberto J. Espay, Nicolas Dupré, Lior Greenbaum, Sharon Hassin-Baer, Guy A. Rouleau, Roy N. Alcalay, Edward A. Fon, and Ziv Gan-Or
JournalNeurobiol Aging
Date Published2020 09
KeywordsAged, alpha-Synuclein, Female, Genetic Association Studies, Genetic Variation, Humans, Intracellular Signaling Peptides and Proteins, Lysosomes, Male, Middle Aged, Negative Results, Niemann-Pick Disease, Type C, Parkinson Disease

Biallelic variants in NPC1, a gene coding for a lysosomal transmembrane protein involved in cholesterol trafficking, may cause Niemann-Pick disease type C (NPC). A few cases of NPC1 variant carriers with Parkinson's disease (PD) have been reported. In addition, pathologic studies have demonstrated phosphorylated alpha-synuclein and Lewy pathology in brains of NPC patients. Therefore, we aimed to examine whether NPC1 genetic variants may be associated with PD. Full sequencing of NPC1 was performed in 2657 PD patients and 3647 controls from 3 cohorts, using targeted sequencing with molecular inversion probes. A total of 9 common variants and 126 rare variants were identified across the 3 cohorts. To examine their association with PD, regression models adjusted for age, sex, and origin were performed for common variants, and optimal sequence Kernel association test (SKAT-O) was performed for rare variants. After correction for multiple comparisons, common and rare NPC1 variants were not associated with PD. Our results do not support a link between heterozygous variants in NPC1 and PD.

Alternate JournalNeurobiol Aging
PubMed ID32371106
PubMed Central IDPMC7302975
Grant ListK02 NS080915 / NS / NINDS NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
FDN 154301 / / CIHR / Canada