Genetic analysis of DNA methylation and hydroxymethylation genes in Parkinson's disease

NEUROBIOLOGY OF AGING

卷:84

Article

Shu, Li¹  Qin, Lixia¹  Min, Shishi²  Pan, Hongxu¹  Zhong, Junfei¹  Guo, Jifeng^1,3,4,5,6,7  Sun, Qiying^3,4,8  Yan, Xinxiang^1,3,4  Chen, Chao²  Tang, Beisha^{1,2,3,4,5,6,7,8}  Xu, Qian^1,3,4 

[1] Cent South Univ, Xiangya Hosp, Dept Neurol, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China

[2] Cent South Univ, Ctr Med Genet, Changsha, Hunan, Peoples R China

[3] Natl Clin Res Ctr Geriatr Disorders, Changsha, Hunan, Peoples R China

[4] Cent South Univ, Key Lab Hunan Prov Neurodegenerat Disorders, Changsha, Hunan, Peoples R China

[5] Beijing Inst Brain Disorders, Parkinsons Dis Ctr, Beijing, Peoples R China

[6] Collaborat Innovat Ctr Brain Sci, Shanghai, Peoples R China

[7] Collaborat Innovat Ctr Genet & Dev, Shanghai, Peoples R China

[8] Cent South Univ, Dept Geriatr, Xiangya Hosp, Changsha, Hunan, Peoples R China

关键词: Parkinson's disease;    DNA methylation;    TET1;    Epigenetic;    Genetic;   

DOI  :  10.1016/j.neurobiolaging.2019.02.025

来源: Elsevier

【 摘 要 】

DNA methylation is an important regulatory mechanism of Parkinson's disease (PD). To investigate the relationship between DNA methylation and hydroxymethylation genes and PD, we performed gene-targeted sequencing using molecular inversion probes in a Chinese PD population. We sequenced 12 genes related to DNA methylation and hydroxymethylation in 1657 patients and 1394 control subjects. We conducted genewise association analyses of rare variants detected in the present study and identified the TET1 gene as important in PD (p = 0.0037738, 0.013, 0.019521 (b.collapse test, variable threshold test, and skat-o test, respectively; sex + age as covariates). However, no positive results were observed when conducting association analyses on common variants in these genes. We performed a comprehensive analysis of associations between variants of DNA methylation and hydroxymethylation genes and PD, resulting in determination that TET1 might play a role in PD. (C) 2019 Elsevier Inc. All rights reserved.

【 授权许可】

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