The protective effect of higher serum TAG (51:4) levels against Parkinson’s disease

Emerging evidence has shown a strong correlation between serum TAG levels, the inflammatory response and Parkinson's disease (PD) onset. However, the causal relationship between TAG levels and PD has not been well established. We aimed to investigate the relationship between serum TAG levels and risk of PD and explore the potential mediating role of circulating immune cells and inflammatory proteins. We utilised genotype data from the GeneRISK cohort, and summary data from genome-wide association studies investigating PD, circulating immune cells, inflammatory proteins and plasma lipidomes. Using Mendelian randomisation (MR) and multivariate MR (MVMR) analysis, we further adjusted for phosphatidylcholine (17:0_18:1) and TAG (58:7). Our results suggested a robust causal link between higher serum TAG (51:4) levels and a decreased risk of PD, with 1 sd genetically instrumented higher serum TAG (51:4) level leading to a 21 per cent (95 % CI 0·66, 0·96) reduction in the risk of PD (<i>P</i>= 0·015). Additionally, the results of the mediation analysis suggested a possible role for mediation through circulating immune cells (including IgD-CD38-B cells and resting CD4 regulatory T cells), but not circulating inflammatory proteins, in the causal relationship between the plasma lipidomes and PD. Our study confirms a causal relationship between higher serum TAG (51:4) levels and a lower risk of PD and clarifies a possible role for mediation through circulating immune cells, but not inflammatory proteins. These findings indicate that serum TAG (51:4) regulates immunity to effectively lower the risk of PD.