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

Li Shu; Lixia Qin; Shishi Min; Hongxu Pan; Junfei Zhong; Jifeng Guo; Qiying Sun; Xinxiang Yan; Chao Chen; Beisha Tang; Qian Xu

doi:10.1016/j.neurobiolaging.2019.02.025

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

Neurobiol Aging. 2019 Dec:84:242.e13-242.e16. doi: 10.1016/j.neurobiolaging.2019.02.025. Epub 2019 Mar 11.

Authors

Li Shu¹, Lixia Qin¹, Shishi Min², Hongxu Pan¹, Junfei Zhong¹, Jifeng Guo³, Qiying Sun⁴, Xinxiang Yan⁵, Chao Chen², Beisha Tang⁶, Qian Xu⁷

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Center for Medical Genetics, Central South University, Changsha, Hunan, China.
³ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China; Parkinson's Disease Center of Beijing Institute for Brain Disorders, Beijing, China; Collaborative Innovation Center for Brain Science, Shanghai, China; Collaborative Innovation Center for Genetics and Development, Shanghai, China.
⁴ National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China; Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁵ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China.
⁶ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Center for Medical Genetics, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China; Parkinson's Disease Center of Beijing Institute for Brain Disorders, Beijing, China; Collaborative Innovation Center for Brain Science, Shanghai, China; Collaborative Innovation Center for Genetics and Development, Shanghai, China; Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁷ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China. Electronic address: 63654097@qq.com.

PMID: 30948140
DOI: 10.1016/j.neurobiolaging.2019.02.025

Abstract

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.

Keywords: DNA methylation; Epigenetic; Genetic; Parkinson's disease; TET1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Methylation*
Humans
Methylation*
Parkinson Disease / genetics*