Genetically determined metabolites in allergic conjunctivitis: A Mendelian randomization study

ElsevierVolume 17, Issue 4, April 2024, 100894World Allergy Organization JournalAuthor links open overlay panel, , AbstractBackground

Allergic conjunctivitis (AC) afflicts a significant portion of the global populace. Yet, its metabolic foundations remain largely unexplored.

Methods

We applied Mendelian Randomization (MR) and Linkage Disequilibrium Score Regression (LDSC) to scrutinize a cohort comprising 20 958 AC cases and 356 319 controls. Data were amalgamated from the metabolomics GWAS server and the FinnGen project, under strict quality control protocols.

Results

Using two-sample MR analysis, 486 blood metabolites were investigated in relation to AC. The IVW approach highlighted 18 metabolites as closely tied to AC risk; of these, 16 retained significance post sensitivity assessments for heterogeneity and horizontal pleiotropy. LDSC analysis, adopted to bolster our findings and negate confounders from shared genetic markers, revealed 8 metabolites with marked heritability, including: palmitate (OR = 0.614), 3-methoxytyrosine (OR = 0.657), carnitine (OR = 1.368), threonate (OR = 0.828), N-[3-(2-Oxopyrrolidin-1-yl)propyl]acetamide (OR = 1.257), metoprolol acid metabolite (OR = 0.982), oleoylcarnitine (OR = 0.635), and 2-palmitoylglycerophosphocholine (OR = 1.351).

Conclusion

AC is precipitated by ocular responses to environmental allergens. Our study unveils a causal link between 8 blood metabolites and AC. This insight accentuates the role of metabolites in AC onset, suggesting novel avenues for its early prediction, targeted prevention, and tailored therapeutic interventions.

Keywords

Allergic conjunctivitis

Metabolites

Mendelian randomization

GWAS

Causal associations

© 2024 The Authors. Published by Elsevier Inc. on behalf of World Allergy Organization.

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