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Metabolomic Insights into COPD: Linking Metabolites, Genes, and Pulmonary Function

Joey Gardner1, Ruifang Li-Gao2, Joseph McGinley1, Ben Molloy1, Emma Quinn1, Nilanjana Sadhu3, Marie Loh3, Kari E. Wong1, John Chambers3. This study leverages Metabolon’s Global Discovery Panel™ to explore the metabolic and genetic drivers of chronic obstructive pulmonary disease (COPD) using data from the large, multi-ethnic HELIOS cohort. Through advanced statistical modeling and Mendelian randomization, researchers identified eight metabolites with causal roles in lung function decline, including markers of oxidative stress, inflammation, and mitochondrial bioenergetics. To go beyond simple associations, the team applied Splash and Ripple, a powerful new network exploration method developed by Metabolon. By mapping direct and indirect connections between metabolites and proteins, Splash and Ripple uncovered key upstream genes and pathways—most notably involving GABA signaling and mucus overproduction—that link environmental stressors like cigarette smoke to impaired pulmonary function. The results highlight how metabolomics can bridge the gap left by genomics by capturing the biochemical effects of both genetic variation and environmental exposures. This integrative approach not only deepens our understanding of COPD biology but also points toward new molecular targets for therapeutic intervention.  
  1.  Metabolon
  2. Leiden University Medical Center
  3. Nanyang Technological University
Identifying-Changes-in-Phytocannabinoid-and-Endocannabinoid-Metabolites

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