Causal association between phenylalanine and Parkinson's disease: a two-sample bidirectional mendelian randomization...

Area of Science:

• Neuroscience
• Genetics
• Metabolic Disorders

Background:

• Emerging evidence suggests a potential link between phenylalanine (Phe) and Parkinson's disease (PD).
• The exact nature of this association, whether direct or indirect, remains to be fully elucidated.

Purpose of the Study:

• To investigate the causal relationship between phenylalanine (Phe) and Parkinson's disease (PD).
• Utilizing a two-sample Mendelian randomization (MR) approach to assess genetic correlations.

Main Methods:

• Downloaded Parkinson's disease (PD) and phenylalanine (Phe) related datasets from the Integrative Epidemiology Unit (IEU) Open GWAS database.
• Employed four distinct algorithms: MR Egger, maximum likelihood, inverse variance weighting (IVW), and unweighted regression for MR analysis.
• Conducted sensitivity analyses, including heterogeneity, horizontal pleiotropy, and Leave-One-Out (LOO) tests, to ensure the robustness of findings.

Main Results:

• Forward MR analysis indicated that phenylalanine (Phe) acts as a protective factor against Parkinson's disease (PD) (p < 0.05, OR < 1).
• Reverse MR analysis revealed no significant causal relationship from PD to Phe (p > 0.05).
• Sensitivity analyses confirmed the reliability and validity of the MR analyses.

Conclusions:

• Phenylalanine (Phe) demonstrates a protective effect, reducing the risk of developing Parkinson's disease (PD).
• This finding supports a potential role for Phe in mitigating PD risk, warranting further investigation.