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Growth Differentiation Factor 15 Is Associated With Alzheimer's Disease Risk.

ABSTRACT:

Background

Previous observational studies have suggested that associations exist between growth differentiation factor 15 (GDF-15) and neurodegenerative diseases. We aimed to investigate the causal relationships between GDF-15 and Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).

Methods

Using summary-level datasets from genome-wide association studies of European ancestry, we performed a two-sample Mendelian randomization (MR) study. Genetic variants significantly associated (p < 5 × 10^-8) with GDF-15 were selected as instrumental variables (n = 5). An inverse-variance weighted method was implemented as the primary MR approach, while weighted median, MR-Egger, leave-one-out analysis, and Cochran's Q-test were conducted as sensitivity analyses. All analyses were performed using R 3.6.1 with relevant packages.

Results

MR provided evidence for the association of elevated GDF-15 levels with a higher risk of AD (odds ratio = 1.14; 95% confidence interval, 1.04-1.24; p = 0.004). In the reverse direction, Mendelian randomization suggested no causal effect of genetically proxied risk of AD on circulating GDF-15 (p = 0.450). The causal effects of GDF-15 on PD (p = 0.597) or ALS (p = 0.120) were not identified, and the MR results likewise did not support the association of genetic liability to PD or ALS with genetically predicted levels of GDF-15. No evident heterogeneity or horizontal pleiotropy was revealed by multiple sensitivity analyses.

Conclusion

We highlighted the role of GDF-15 in AD as altogether a promising diagnostic marker and a therapeutic target.

SUBMITTER: Wu PF

PROVIDER: S-EPMC8414585 | biostudies-literature |

REPOSITORIES: biostudies-literature

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