Mendelian randomization study on the association of circulating ketone bodies with lung cancer and respiratory diseases DOI Creative Commons

Xisha Tang,

Huijia Zhuang,

Hai Yu

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 4, 2024

The liver produces various ketone bodies (KBs) including 3-Hydroxybutyrate (3-OHB), acetoacetate (AcAc), and acetone, with 3-OHB being the major component. Previous studies have shown that KBs protect against respiratory diseases; however, there is no evidence of a genetic link. To avoid biases existing in traditional observational studies, two-sample Mendelian randomization (MR) analysis was carried out to investigate causation novel therapeutic uses for KBs. This study used databases from genome-wide association (GWAS) single nucleotide polymorphisms as instrumental variables recently published metabonomics (n = 121,584) diseases [lung cancer, n 85,716; asthma, 127,669; chronic bronchitis, 450,422; obstructive pulmonary disease (COPD), 468,475; FEV1/FVC < 0.7, 353,315] their publicly available GWAS, respectively. Strong sets (P 5 × 10− 8) were selected, inverse-variance weighted primary MR method. Sensitivity analyses included Cochran's Q test, Egger, MR-PRESSO, leave-one-out funnel plots. Steiger test reversed exclude reverse causality. Additionally, independent replication conducted using another large public GWAS similar methods described above. After sensitivity filtering, we discovered protective effect on lung cancer (odds ratio [OR] 0.771; 95% confidence interval [CI] 0.648–0.916; PFDR=0.006), small cell carcinoma (OR 0.485, CI 0.301–0.781, asthma 0.585, 0.395–0.867, PFDR=0.010), bronchitis 0.753, 0.570–0.994, PFDR=0.045), COPD 0.690, 0.535–0.890, PFDR=0.008) function 0.970, 95%CI 0.950–0.990, PFDR =0.008). In summary, our findings suggest acts factor diseases. However, heterogeneity implies other mechanisms may also be involved improvement by 3-OHB.

Language: Английский

Mendelian randomization study on the association of circulating ketone bodies with lung cancer and respiratory diseases DOI Creative Commons

Xisha Tang,

Huijia Zhuang,

Hai Yu

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 4, 2024

The liver produces various ketone bodies (KBs) including 3-Hydroxybutyrate (3-OHB), acetoacetate (AcAc), and acetone, with 3-OHB being the major component. Previous studies have shown that KBs protect against respiratory diseases; however, there is no evidence of a genetic link. To avoid biases existing in traditional observational studies, two-sample Mendelian randomization (MR) analysis was carried out to investigate causation novel therapeutic uses for KBs. This study used databases from genome-wide association (GWAS) single nucleotide polymorphisms as instrumental variables recently published metabonomics (n = 121,584) diseases [lung cancer, n 85,716; asthma, 127,669; chronic bronchitis, 450,422; obstructive pulmonary disease (COPD), 468,475; FEV1/FVC < 0.7, 353,315] their publicly available GWAS, respectively. Strong sets (P 5 × 10− 8) were selected, inverse-variance weighted primary MR method. Sensitivity analyses included Cochran's Q test, Egger, MR-PRESSO, leave-one-out funnel plots. Steiger test reversed exclude reverse causality. Additionally, independent replication conducted using another large public GWAS similar methods described above. After sensitivity filtering, we discovered protective effect on lung cancer (odds ratio [OR] 0.771; 95% confidence interval [CI] 0.648–0.916; PFDR=0.006), small cell carcinoma (OR 0.485, CI 0.301–0.781, asthma 0.585, 0.395–0.867, PFDR=0.010), bronchitis 0.753, 0.570–0.994, PFDR=0.045), COPD 0.690, 0.535–0.890, PFDR=0.008) function 0.970, 95%CI 0.950–0.990, PFDR =0.008). In summary, our findings suggest acts factor diseases. However, heterogeneity implies other mechanisms may also be involved improvement by 3-OHB.

Language: Английский

Citations

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