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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Causal relationship between fatty acid metabolism and allergic asthma: a mendelian randomization and multi-omics
ShangRao Mo1,2, JinYue Wang3,4, Xiao Li5
1Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, Nanchong, China.
Objective:
Allergic asthma (AAS) arises from intricate gene-environment interactions, yet its pathophysiological mechanisms remain incompletely understood. This study employs a multi-omics approach to elucidate the regulatory role of metabolites in AAS pathogenesis, aiming to identify novel therapeutic targets and preventive strategies.
Methods:
We conducted bidirectional two-sample Mendelian randomization (MR) analysis on 1,400 serum metabolites, followed by co-localization analysis to validate shared genetic loci. Metabolic pathway enrichment focusing on rate-limiting enzymes was performed, complemented by protein-protein interaction (PPI) network construction. MR was systematically applied to assess the impact of 17 lifestyle factors on AAS-associated metabolites.
Results:
Six metabolites including Carnitine C14 (OR = 2.660) and 3-hydroxyoleoylcarnitine (OR = 1.620) showed significant associations with AAS after false discovery rate (FDR) correction (FDR < 0.05). Co-localization analysis (PPH3 + PPH4 > 0.9) identified fatty acid metabolism as the central pathway, with ACACB demonstrating significant interaction with salbutamol's target ADRB3. Lifestyle modulation analysis revealed cereal intake suppressed Carnitine C14 metabolism (p = 0.007), while cheese (p = 0.029) and oily fish consumption (p = 0.015) regulated 3-hydroxyoleoylcarnitine levels.
Conclusions:
This multi-omics integration study pioneers in delineating fatty acid metabolic reprogramming as a central mechanism in AAS pathogenesis. The identified ACACB-ADRB3 axis presents a novel therapeutic target, while dietary modulations of metabolite profiles offer promising avenues for personalized prevention strategies, advancing precision medicine in asthma management.
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