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Causal effect of gut microbiota-derived metabolite trimethylamine N-oxide on Parkinson’s disease: A Mendelian randomisation study

Eur J Neurol. 2023 Jan 24. doi: 10.1111/ene.15702. Online ahead of print.


BACKGROUND: It has been suggested that trimethylamine N-oxide (TMAO) is related to Parkinson’s disease (PD) in observational studies. However, the direction of this association is inconsistent. An exploratory Mendelian randomisation study was conducted to investigate whether TMAO and its precursors have a causal relationship with PD.

METHODS: We obtained summary statistics for single nucleotide polymorphisms related to circulating levels of TMAO, betaine, carnitine, choline, and the corresponding data for the risk, age at onset, and progression of PD from the genome-wide association studies. Inverse variance weighting was used as the primary method for effect estimation. The false discovery rate (FDR) was applied to the correction of multiple testing. The P-value of association < 0.05 but above the FDR-corrected threshold was deemed suggestive evidence of a possible association. A range of robust MR methods were used for sensitivity analysis.

RESULTS: We observed suggestive evidence of inverse causal effect of TMAO on motor fluctuations (OR=0.851, 95%CI (0.731,0.990), P=0.037) and carnitine on insomnia (OR=0.817, 95%CI (0.700,0.954), P=0.010), and positive causal effect of betaine on Hoehn-Yahr stage (OR=1.397, 95%CI (1.112,1.756), P=0.004), Unified Parkinson’s Disease Rating Scale (UPDRS) III score (β=0.138, 95%CI (0.051,0.225), P=0.002), motor fluctuations (OR=1.236, 95%CI (1.011,1.511), P=0.039), and choline on UPDRS IV (β=0.106, 95%CI (0.026,0.185), P=0.009) and modified Schwab and England Activities of Daily Living Scale score (β=0.806, 95%CI (0.127,1.484), P=0.020).

CONCLUSIONS: Our findings provide suggestive evidence that TMAO and its precursors have a causal effect on the progression of PD. Further investigation of the underlying mechanisms is required.

PMID:36692876 | DOI:10.1111/ene.15702

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