Exploring the causal link between serum amino acids and Parkinson's disease: a Mendelian randomization approach

Abstract

This study aimed to explore the causal relationships between multiple blood amino acids (BAAs) and the Parkinson's disease (PD). We downloaded genome-wide association study (GWAS) data for BAAs and PD from the OpenGWAS database, screened single nucleotide polymorphisms (SNPs) from the data, and evaluated the causal relationship between BAA levels and PD using the inverse variance weighted (IVW) method. The sensitivity analysis was also conducted. After SNP screening, three amino acid indicators were identified: met-a-308 (phenylalanine), met-a-584 (X-12100 hydroxytryptophan), and met-a-337 (5-hydroxyproline), which showed significant causal relationship with the occurrence of PD. There was no significant heterogeneity or horizontal pleiotropy, and the results were stable. The multivariate MR analysis showed that the mediating effects generated by the introduction of multiple variables were not significant. In conclusion, phenylalanine, X-12,100 hydroxytryptophan, and 5-hydroxyproline have a causal relationship with the occurrence of PD and may be potential early screening biomarkers and blocking targets.

Fig. 1

A. Schematic diagram of multivariate Mendelian randomization and mediation analysis. The basic assumptions of Mendelian randomization analysis include (1) the assumption of relevance, which states that the selected instrumental variable must be significantly correlated with the exposure factor; (2) The assumption of independence, which states that instrumental variables must have no significant correlation with potential confounding factors that may affect exposure or outcome; (3) Exclusivity limitation means that instrumental variables can only affect outcomes through the path of “instrumental variables → exposure → outcome”. B. The analytic process in this study. (SNP, single nucleotide polymorphism. IVW, inverse variance weighted. MR, Mendelian randomization. GWAS, genome-wide association study. LD, Linkage disequilibrium.)

Fig. 2

Mendelian randomization analysis of the causal relationship between Blood amino acid index Iron and Parkinson’s disease (PD). (A). Blood amino acids (Blood amino acid index) of Parkinson’s disease (Parkinson 's diseases, the pathogenesis of PD) Mendelian randomization of the results of the analysis of forest graph display. (B) - d. Blood amino acids (Blood amino acid index) met - a - 308 (B), met - a - 337 (C), met - a - 584 (D) and Parkinson’s disease (Parkinson 's diseases, The results of Mendelian randomization analysis between PD) are shown in scatter plots. (E) - g. Blood amino acids (Blood amino acid index) met - a - 308 (E), met - a - 337 (F), met - a - 584 (G) and Parkinson’s disease (Parkinson 's diseases, Funnel plot showing the heterogeneity test of the results of Mendelian randomization analysis of causality between PD). (H)-(j). Blood amino acid index met-a-308 (H), met-a-337(I), met-a-584(J) and Parkinson’s disease (PD, P < 0.05). PD) using a single SNP loci analysis of the causal relationship between each effect of estimated results of forest.

Fig. 3

Parkinson’s disease (Parkinson 's diseases, PD) and amino acid of Blood (Blood amino acid index) between Iron causality analysis of the Mendelian randomization. Forest plot of the results of Mendelian randomization analysis of Blood amino acid indexes met-a-308, met-a-337, met-a-584 for Parkinson’s disease (PD).