Association Analysis of Essential Tremor-Associated Genetic Variants in Sporadic Late-Onset Parkinson's Disease

Sheng Zeng; Xun Zhou; Runcheng He; Yuwen Zhao; Zhenhua Liu; Qian Xu; Jifeng Guo; Xinxiang Yan; Jinchen Li; Beisha Tang; Qiying Sun

doi:10.5334/tohm.885

Association Analysis of Essential Tremor-Associated Genetic Variants in Sporadic Late-Onset Parkinson's Disease

Tremor Other Hyperkinet Mov (N Y). 2024 May 10:14:25. doi: 10.5334/tohm.885. eCollection 2024.

Authors

Sheng Zeng^{1

2}, Xun Zhou³, Runcheng He⁴, Yuwen Zhao⁴, Zhenhua Liu^{2

4

5}, Qian Xu^{2

4

5}, Jifeng Guo^{2

4

5}, Xinxiang Yan^{2

4

5}, Jinchen Li^{2

3

5}, Beisha Tang^{2

3

4

5

6}, Qiying Sun^{2

4

5

6}

Affiliations

¹ Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
² Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, 410008, China.
³ Department of Geriatric Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
⁴ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
⁵ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
⁶ Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, 410008, China.

Abstract

Background: Parkinson's disease (PD) and Essential tremor (ET) are the two most common tremor diseases with recognized genetic pathogenesis. The overlapping clinical features suggest they may share genetic predispositions. Our previous study systematically investigated the association between rare coding variants in ET-associated genes and early-onset PD (EOPD), and found the suggestive association between teneurin transmembrane protein 4 (TENM4) and EOPD. In the current research, we explored the potential genetic interplay between ET-associated genetic loci/genes and sporadic late-onset PD (LOPD).

Methods: We performed whole-genome sequencing in the 1962 sporadic LOPD cases and 1279 controls from mainland China. We first used logistic regression analysis to test the top 16 SNPs identified by the ET genome-wide association study for the association between ET and LOPD. Then we applied the optimized sequence kernel association testing to explore the rare variant burden of 33 ET-associated genes in this cohort.

Results: We did not observe a significant association between the included SNPs with LOPD. We also did not discover a significant burden of rare deleterious variants of ET-associated genes in association with LOPD risk.

Conclusion: Our results do not support the role of ET-associated genetic loci and variants in LOPD.

Highlights: 1962 cases and 1279 controls were recruited to study the potential genetic interplay between ET-associated genetic loci/variants and sporadic LOPD.No significant association between the ET-associated SNPs and LOPD were observed.No significant burden of rare deleterious variants of ET-associated gene in LOPD risk were found.

Keywords: Parkinson’s disease; SKAT-O; association analysis; essential tremor; genetic variant; rare deleterious variants.

Publication types

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

MeSH terms

Age of Onset
Aged
Case-Control Studies
China
Essential Tremor* / genetics
Female
Genetic Predisposition to Disease* / genetics
Genome-Wide Association Study*
Humans
Male
Middle Aged
Parkinson Disease* / genetics
Polymorphism, Single Nucleotide* / genetics

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (U20A20355, 82171256, 82202051), Natural Science Foundation of Hunan Province, China (2021JJ40819) and the Scientific Research Launch Project for new employees of the Second Xiangya Hospital of Central South University.