Variants in the Niemann-Pick type C gene NPC1 are not associated with Parkinson's disease

Neurobiol Aging. 2020 Sep;93:143.e1-143.e4. doi: 10.1016/j.neurobiolaging.2020.03.021. Epub 2020 Apr 8.


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.

Keywords: Lysosomal genes; NPC1; Niemann–Pick disease type C; Parkinson's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Genetic Association Studies*
  • Genetic Variation*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Lysosomes / genetics
  • Male
  • Middle Aged
  • Negative Results*
  • Niemann-Pick Disease, Type C / genetics*
  • Niemann-Pick Disease, Type C / metabolism
  • Parkinson Disease / genetics*
  • alpha-Synuclein


  • Intracellular Signaling Peptides and Proteins
  • NPC1 protein, human
  • alpha-Synuclein