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

To conduct a meta-analysis investigating the relationship between the chromosome 9 open reading frame 72 () 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 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). 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 repeat expansions (>30) were not associated with the risk of PD (OR = 1.51, 95% CI = 0.55-4.17), intermediate repeat expansions (20-30) were indeed associated with PD (OR = 2.43, 95% CI = 1.20-4.9). The pathological mechanism of G4C2 repeat expansions differs across various NDs due to the varying number of pathogenic expansions. Measuring the number of G4C2 repeats may be useful in the early-stage differential diagnosis of various NDs.