Genetic meta-analysis of levodopa induced dyskinesia in Parkinson’s disease

Output Details

Preprint May 30, 2023

Published August 30, 2023

The genetic basis of levodopa-induced-dyskinesia (LiD) is poorly understood, and there have been few well-powered genome-wide studies. We performed a genome-wide survival meta-analyses to study the effect of genetic variation on the development of LiD in five separate longitudinal cohorts, and meta-analysed the results. We included 2784 PD patients, of whom 14.6% developed LiD. Based on a functional annotation analysis on chromosome 1, we determined that changes in DNAJB4 gene expression, close to LRP8, are an additional potential cause of increased susceptibility to LiD. Baseline anxiety status was significantly associated with LiD (OR = 1.14, SE = 0.03, P = 7.4 × 10−5). We performed a candidate variant analysis of previously reported loci, and found that genetic variability in ANKK1 (rs1800497, HR = 1.27, SE = 0.09, P = 8.89 × 10−3) and BDNF (rs6265, HR = 1.21, SE = 0.10, P = 4.95 × 10−2) loci were significantly associated with time to LiD in our large meta-analysis.
Tags
  • Dyskinesia
  • Genetic variants
  • GWAS
  • Levodopa
  • Meta-analysis
  • Original Research

Meet the Authors

  • Alejandro Martínez Carrasco, MSc

    Key Personnel: Team Hardy

    University College London

  • User avatar fallback logo

    Raquel Real, PhD

    Key Personnel: Team Hardy

    University College London

  • User avatar fallback logo

    Michael Lawton

  • User avatar fallback logo

    Hirotaka Iwaki

  • User avatar fallback logo

    Manuela Tan

  • Lesley Wu, MSc

    Key Personnel: Team Hardy

    University College London

  • User avatar fallback logo

    Nigel Williams

  • User avatar fallback logo

    Camille Carroll

  • User avatar fallback logo

    Michele T.M. Hu

  • User avatar fallback logo

    Donald Grosset

  • John Hardy, PhD

    Lead PI (Core Leadership): Team Hardy

    University College London

  • Mina Ryten

    Co-PI (Core Leadership): Team Hardy Team Wood

    University College London

  • User avatar fallback logo

    Tom Foltynie

  • User avatar fallback logo

    Yoav Ben-Shlomo

  • User avatar fallback logo

    Maryam Shoai, PhD

    Key Personnel: Team Hardy

    University College London

  • Huw Morris

    Collaborating PI: Team Hardy

    University College London