A Mendelian randomization study on associations between plasma lipidome, circulating inflammatory proteins, and...

Area of Science:

• Biochemistry
• Genetics
• Medicine

Background:

• Emerging evidence suggests a link between plasma lipidome and erectile dysfunction (ED).
• The precise mechanisms and the role of inflammatory proteins as mediators remain poorly understood.
• This study aims to clarify the causal relationships involving plasma lipidome, inflammatory proteins, and ED.

Purpose of the Study:

• To investigate the potential causal relationships between plasma lipidome and ED.
• To explore the role of circulating inflammatory proteins as mediators in ED.
• To utilize Mendelian randomization to assess these complex interactions.

Main Methods:

• Employed bidirectional two-sample Mendelian randomization (MR) using large-scale genome-wide association study (GWAS) data.
• Utilized inverse variance weighted (IVW) as the primary analysis method, with MR-Egger and weighted median as supplementary.
• Conducted sensitivity analyses (PRESSO, Cochran's Q, MR-Egger intercept) to ensure robustness against heterogeneity and pleiotropy.

Main Results:

• Specific ceramides and triacylglycerols were associated with increased ED risk, while certain phosphatidylethanolamines and phosphatidylinositols were linked to decreased risk.
• Identified several inflammatory proteins (e.g., IL-1α, TNF-SF9) positively associated with ED, and others (e.g., LIF, uPA) negatively associated.
• Mediation analysis demonstrated that urokinase-type plasminogen activator (uPA) mediates the effect of Triacylglycerol (56:3) on ED.

Conclusions:

• Established a causal relationship between plasma lipidome, circulating inflammatory proteins, and ED.
• Confirmed that circulating inflammatory proteins, specifically uPA, act as mediators in the pathway from triacylglycerol levels to ED.