Meta-analysis of the association between C9orf72 repeats and neurodegeneration diseases

Abstract

To conduct a meta-analysis investigating the relationship between the chromosome 9 open reading frame 72 (C9orf72) GGGGCC (G4C2) and neurodegenerative diseases (NDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We searched the EMBASE, PubMed, Web of Science, and Cochrane databases. Twenty-seven case-control studies were included, comprising 7202 AD, 5856 PD, 644 MSA, 439 PSP, and 477 CBD cases. This study demonstrated that C9orf72 repeat expansions (>30) were associated with AD, MSA, PSP, and CBD (AD: OR = 4.88, 95% CI = 2.71–8.78; MSA: OR = 6.98, 95% CI = 1.48-33.01; PSP: OR =10.04, 95% CI = 2.72-37.10; CBD: OR = 28.04, 95% CI = 10.17-77.31). C9orf72 intermediate repeat expansions (20–30) were not associated with AD and MSA (AD: OR = 1.16, 95% CI = 0.39–3.45; MSA: OR = 5.65, 95% CI = 0.69–46.19), while C9orf72 repeat expansions (>30) were not associated with the risk of PD (OR = 1.51, 95% CI = 0.55–4.17), C9orf72 intermediate repeat expansions (20–30) were indeed associated with PD (OR = 2.43, 95% CI = 1.20–4.9). The pathological mechanism of C9orf72 G4C2 repeat expansions differs across various NDs due to the varying number of pathogenic expansions. Measuring the number of C9orf72 G4C2 repeats may be useful in the early-stage differential diagnosis of various NDs.

Keywords:

• Alzheimer’s disease
• Parkinson’s disease
• progressive supranuclear palsy
• corticobasal degeneration
• multiple system atrophyC9orf72 repeat
• meta-analysis

Acknowledgements

We would like to express our gratitude to all those who helped us during the writing of this manuscript. We gratefully acknowledge the help of the professor, Ms. Shuyan Cong, who has offered us valuable suggestions in the academic studies. In the preparation of the thesis, she has spent much time reading through each draft and provided us with inspiring advice. We also thank Mr. Liqiang Zheng for graphical assistance. We would finally like to express our gratitude to our beloved parents, who have always been helping us out of difficulties and supporting us without a word of complaint.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.