Genetic meta-analysis of levodopa induced dyskinesia in Parkinson’s disease
Published August 30, 2023
Output Details
Preprint May 30, 2023
Published August 30, 2023
Description
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.
Identifier (DOI)
10.1038/s41531-023-00573-2
