Association between circulating fatty acid metabolites and asthma risk: a two-sample bidirectional Mendelian...

Area of Science:

• Immunology
• Genetics
• Nutritional Science

Background:

• Fatty acids play a role in human immune responses.
• Polyunsaturated fatty acid (PUFA) supplementation may alleviate asthma symptoms, but their direct impact on asthma risk is debated.

Purpose of the Study:

• To investigate the causal relationship between serum fatty acids and asthma risk using Mendelian Randomization (MR).

Main Methods:

• Utilized two-sample bidirectional MR analysis with genetic variants for 123 fatty acid metabolites and asthma GWAS data.
• Employed inverse-variance weighted, weighted median, and MR-Egger regression methods.
• Performed multivariable MR, reverse MR, cis-eQTL-MR, and colocalization analyses to assess pleiotropy and gene expression associations.

Main Results:

• Higher average methylene groups in fatty acids were linked to lower asthma risk, while increased bis-allylic groups correlated with higher risk.
• These associations disappeared when FADS1 gene-correlated SNPs were excluded.
• Colocalization and cis-eQTL-MR analyses indicated shared causal variants between FADS1 expression and asthma risk.

Conclusions:

• The observed association between PUFA traits and asthma risk is primarily influenced by FADS1 gene polymorphisms.
• Results highlight the importance of considering gene-environment interactions and pleiotropy in fatty acid-asthma research.