Assessment of LIN28A variants in Parkinson's disease in large European cohorts

Neurobiol Aging. 2021 Apr:100:118.e1-118.e3. doi: 10.1016/j.neurobiolaging.2020.12.002. Epub 2020 Dec 11.

Abstract

Parkinson's disease (PD) is a complex neurodegenerative disease with a strong genetic component. To date, several genes have been associated with monogenic forms of the disease, but these only explain a small fraction of the observed familial aggregation in PD. Recently, a heterozygous loss-of-function variant in LIN28A was associated with PD pathogenesis in the Asian population. Here, we comprehensively investigate the role of LIN28A variants in PD patients of European ancestry and assess susceptibility using individual-level genotyping data from 14,671 PD cases and 17,667 controls, as well as whole-genome sequencing data from 1647 patients with PD and 1050 controls. In addition, we further assess the summary statistics from the most recent genome-wide association studies meta-analyses to date for PD risk and age at onset. After evaluating these data, we did not find evidence to support a role for LIN28A as a major causal gene for PD. However, additional large-scale familial and case-control studies in non-European ancestry populations are necessary to further evaluate the role of LIN28A in PD etiology.

Keywords: LIN28A; Loss of function; Parkinson's disease; Risk factor.

Publication types

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

MeSH terms

  • Age of Onset
  • Aged
  • Cohort Studies
  • Data Interpretation, Statistical
  • Databases, Genetic
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study*
  • Humans
  • Loss of Function Mutation / genetics*
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Negative Results*
  • Parkinson Disease / epidemiology
  • Parkinson Disease / genetics*
  • RNA-Binding Proteins / genetics
  • Risk Factors
  • White People / genetics

Substances

  • Lin28A protein, human
  • RNA-Binding Proteins