利用血液代谢物识别呼吸系统疾病的遗传因素OA

Genome-wide association study(GWAS)data are used to explore the associations between blood metabolites and 5 re-spiratory 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,in-cluding MR-Egger regression,the weighted median,the weighted mode,Cochran's Q test,and the pleiotropy test.Additional direc-tional 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'-diphos-phate(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.