Glutamine and allergic rhinitis: A bidirectional two-sample Mendelian randomization study

Area of Science:

• Genetics and Epidemiology
• Nutritional Science
• Immunology

Background:

• Allergic rhinitis (AR) is a prevalent condition with complex etiology.
• Glutamine (Gln) has been suggested as a potential protective factor in AR, but causal links are not well-established.
• Understanding the relationship between Gln levels and AR risk is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate the potential causal association between circulating glutamine (Gln) levels and the risk of allergic rhinitis (AR) using a bidirectional Mendelian randomization (MR) approach.
• To determine if Gln is a protective factor against AR or if AR influences Gln levels.
• To confirm findings through robust sensitivity analyses and phenotypic association scanning.

Main Methods:

• Bidirectional two-sample Mendelian randomization (MR) analysis utilizing genome-wide association study (GWAS) summary statistics for AR and Gln levels.
• Inverse variance weighted (IVW) method as the primary analysis, supplemented by weighted median, simple median, and MR-Egger sensitivity analyses.
• Heterogeneity tests, MR-Egger intercept test for horizontal pleiotropy, and leave-one-out (LOO) analysis were performed to ensure robustness.

Main Results:

• Forward MR analysis (Gln → AR) demonstrated a significant negative causal association, indicating that higher Gln levels protect against AR (IVW OR < 1, P < .05).
• Reverse MR analysis (AR → Gln) showed no evidence of a causal effect of AR on Gln levels (P > .05).
• Sensitivity analyses, including heterogeneity and pleiotropy tests, confirmed the reliability and stability of the findings. Phenotypic association scanning also supported Gln's protective role.

Conclusions:

• Glutamine (Gln) is causally associated with a reduced risk of allergic rhinitis (AR), establishing Gln as a protective factor.
• Allergic rhinitis (AR) does not appear to have a causal effect on circulating glutamine (Gln) levels.
• These findings support the potential therapeutic role of glutamine in managing or preventing allergic rhinitis.