Genomic Analysis Identifies New Loci Associated With Motor Complications in Parkinson's Disease

Ho Sung Ryu, Kye Won Park, Nari Choi, Jinhee Kim, Young Min Park, Sungyang Jo, Mi Jung Kim, Young Jin Kim, Juyeon Kim, Kiju Kim, Seong Beom Koh, Sun Ju Chung

Research output: Contribution to journalArticle

Abstract

Background: Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by a clinical symptomatology involving both motor and non-motor symptoms. Motor complications associated with long-term dopaminergic treatment include motor fluctuations and levodopa-induced dyskinesia (LID), which may have a major impact on the quality of life. The clinical features and onset time of motor complications in the disease course are heterogeneous, and the etiology remains unknown. Objective: We aimed to identify genomic variants associated with the development of motor fluctuations and LID at 5 years after the onset of PD. Methods: Genomic data were obtained using Affymetrix Axiom KORV1.1 array, including an imputation genome-wide association study (GWAS) grid and other GWAS loci; functional variants of the non-synonymous exome; pharmacogenetic variants; variants in genes involved in absorption, distribution, metabolism, and excretion of drugs; and expression quantitative trait loci in 741 patients with PD. Results: FAM129B single-nucleotide polymorphism (SNP) rs10760490 was nominally associated with the occurrence of motor fluctuations at 5 years after the onset of PD [odds ratio (OR) = 2.9, 95% confidence interval (CI) = 1.8–4.8, P = 6.5 × 10−6]. GALNT14 SNP rs144125291 was significantly associated with the occurrence of LID (OR = 5.5, 95% CI = 2.9–10.3, P = 7.88 × 10−9) and was still significant after Bonferroni correction. Several other genetic variants were associated with the occurrence of motor fluctuations or LID, but the associations were not significant after Bonferroni correction. Conclusion: This study identified new loci associated with the occurrence of motor fluctuations and LID at 5 years after the onset of PD. However, further studies are needed to confirm our findings.

Original languageEnglish
Article number570
JournalFrontiers in Neurology
Volume11
DOIs
Publication statusPublished - 2020 Jul 7

Keywords

  • Parkinson's disease
  • genome-wide association study
  • genomic variants
  • levodopa-induced dyskinesia
  • motor fluctuations

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Ryu, H. S., Park, K. W., Choi, N., Kim, J., Park, Y. M., Jo, S., Kim, M. J., Kim, Y. J., Kim, J., Kim, K., Koh, S. B., & Chung, S. J. (2020). Genomic Analysis Identifies New Loci Associated With Motor Complications in Parkinson's Disease. Frontiers in Neurology, 11, [570]. https://doi.org/10.3389/fneur.2020.00570