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

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

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00570

DOI=10.3389/fneur.2020.00570

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Objective:</bold> We aimed to identify genomic variants associated with the development of motor fluctuations and LID at 5 years after the onset of PD.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold><italic>FAM129B</italic> 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, <italic>P</italic> = 6.5 × 10<sup>−6</sup>]. <italic>GALNT14</italic> SNP rs144125291 was significantly associated with the occurrence of LID (OR = 5.5, 95% CI = 2.9–10.3, <italic>P</italic> = 7.88 × 10<sup>−9</sup>) 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.</p><p><bold>Conclusion:</bold> 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.</p>