Genetically supported causality between alcohol dependence, immune cells and opioids tolerance: A two-sample...

Area of Science:

• Genetics
• Immunology
• Pharmacology

Background:

• Previous studies suggest links between alcohol consumption, immune cells, and opioid tolerance.
• Causal relationships remain unclear.

Purpose of the Study:

• To investigate the causal relationship between alcohol dependence, immune cells, and opioid tolerance using Mendelian randomization.
• To explore the mediating role of immune cells in the association between alcohol dependence and opioid tolerance.

Main Methods:

• Two-sample Mendelian randomization analysis.
• Inverse variance weighting (IVW) as the primary method.
• Sensitivity analyses including MR-Egger, MR-PRESSO, and leave-one-out analyses were performed.

Main Results:

• Alcohol dependence showed a causal association with increased opioid tolerance (OR=1.057, P=0.008).
• Absolute monocyte count was identified as a mediator between alcohol dependence and opioid tolerance (OR=1.002, P=0.044), accounting for 3.6% mediation.
• Causal relationships were observed between 33 types of immune cells and opioid tolerance.

Conclusions:

• Genetic evidence supports alcohol dependence as a promoter of opioid tolerance.
• Increased monocyte counts may mediate this effect, highlighting the immune system as a potential therapeutic target.
• Findings offer insights for developing novel prevention strategies for opioid tolerance.