Journal
NEUROBIOLOGY OF AGING
Volume 93, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2020.03.018
Keywords
Parkinson's disease; N6-methyladenosine; Methylation; Epigenetic; Genetic
Categories
Funding
- National Natural Science Foundation of China [81430023, 81401059, 81361120404]
- National Key Plan for Scientific Research and Development of China [2016YFC1306000, 2017YFC0909100]
- Science and Technology Major Project of Hunan Province [2018SK1030]
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Parkinson's disease (PD) is a common neurodegenerative disease with a relatively unclear etiology. Previous studies have shown that N6-methyladenosine (m6A) is a vital RNA modification enriched in brain tissue, and that the genes involved in m6A modification are implicated in various neurologic diseases. Here, we conducted a comprehensive genetic analysis using targeted sequencing with molecular inversion probes (MIPs) to identify m6A-modification genes (including METTL3, MEITL14, VVTAP, FTO, ALKBH5, YTHDF1, YTHDF2, YTHDF3, HNRNPC, and ELAVL1) in a total of 1647 sporadic PD patients and 1372 controls of Han Chinese origin. PD patients were divided into early-onset PD (EOPD) and late-onset PD (LOPD) based on whether the onset of motor symptoms occurred before or after 50 years of age. Rare variants were subjected to gene-based burden tests and common variants were subjected to single-variant association analyses. As a result, we identified 214 rare variants in all 10 m6A-modification genes and 16 common variants in 7 genes. Gene-wise association analyses of rare variants in each m6A-modification gene did not achieved a p value of less than 0.05 in either total cohorts or 2 age groups. In fact, p values greater than 0.05 were found when conducting single-variant association analyses on common variants of these genes between PD and control patients. Our comprehensive analyses of m6A-modification genes suggest that there is no significant association between these 10 m6A-modification genes and the risk of sporadic PD. (C) 2020 Elsevier Inc. All rights reserved.
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