Using Blood Metabolites to Identify Genetic Factors in Respiratory Disease

Genome-wide association study (GWAS) data are used to explore the associations between blood metabolites and 5 respiratory diseases: asthma, tuberculosis (TB), chronic obstructive pulmonary disease (COPD), cor pulmonale, and bronchitis. The main method of analysis used is the inverse-variance weighted (IVW) approach, complemented by several sensitivity analyses, including MR-Egger regression, the weighted median, the weighted mode, Cochran's Q test, and the pleiotropy test. Additional directional tests, Meta-analysis and metabolic pathway analyses are conducted for deeper insights. 3 metabolites showing significant causal relationships are identified. Catechol glucuronide levels as a protective factor have a positive causal relationship with asthma; the creatine to carnitine ratio has a negative causal relationship with COPD as a risk factor; and the adenosine 5'-diphosphate (ADP) to N-acetylglucosamine to N-acetylgalactosamine ratio as a protective factor has a positive causal relationship with bronchitis. Additionally, 13 metabolites demonstrate strong causal relationships. Furthermore, we delineate 14 metabolic pathways related to the outcomes, including 6 associated with asthma, 2 with TB, 1 with COPD, 4 with cor pulmonale, and 1 with bronchitis. A causal relationship between blood metabolites and 5 respiratory diseases has been established. The identified metabolites and pathways offer new insights into the underlying mechanisms of these diseases, necessitating further experimental validation.