Comprehensive assessment of PINK1 variants in Parkinson's disease

Neurobiol Aging. 2020 Jul:91:168.e1-168.e5. doi: 10.1016/j.neurobiolaging.2020.03.003. Epub 2020 Mar 10.

Abstract

Multiple genes have been associated with monogenic Parkinson's disease and Parkinsonism syndromes. Mutations in PINK1 (PARK6) have been shown to result in autosomal recessive early-onset Parkinson's disease. In the past decade, several studies have suggested that carrying a single heterozygous PINK1 mutation is associated with increased risk for Parkinson's disease. Here, we comprehensively assess the role of PINK1 variants in Parkinson's disease susceptibility using several large data sets totalling 376,558 individuals including 13,708 cases with Parkinson's disease and 362,850 control subjects. After combining these data, we did not find evidence to support a role for heterozygous PINK1 mutations as a robust risk factor for Parkinson's disease.

Keywords: Heterozygous carriers; PINK1; Parkinson's disease; Risk factor; p.G411S.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Datasets as Topic*
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease / genetics*
  • Heterozygote
  • Humans
  • Male
  • Membrane Proteins
  • Middle Aged
  • Mutation*
  • Negative Results*
  • Parkinson Disease / genetics*
  • Parkinsonian Disorders / genetics*
  • Protein Kinases / genetics*
  • Risk Factors
  • Tumor Suppressor Proteins

Substances

  • Membrane Proteins
  • TMEM158 protein, human
  • Tumor Suppressor Proteins
  • Protein Kinases
  • PTEN-induced putative kinase