Lipid-lowering drug targets associated with risk of respiratory disease: a Mendelian randomization study

Abstract Background Observational studies have identified a possible connection between lipid-lowering medications and respiratory illnesses. However, it remains unclear whether lipid-lowering drugs is causative for respiratory diseases, and we aimed to answer this question. Methods We performed Men...

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Main Authors: Zhipeng Gong, Dongsheng Wu, Yin Ku, Congyao Zou, Lin Qiu, Xiaohu Hao, Lunxu Liu
Format: Article
Language:English
Published: BMC 2025-02-01
Series:BMC Pulmonary Medicine
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Online Access:https://doi.org/10.1186/s12890-025-03527-x
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author Zhipeng Gong
Dongsheng Wu
Yin Ku
Congyao Zou
Lin Qiu
Xiaohu Hao
Lunxu Liu
author_facet Zhipeng Gong
Dongsheng Wu
Yin Ku
Congyao Zou
Lin Qiu
Xiaohu Hao
Lunxu Liu
author_sort Zhipeng Gong
collection DOAJ
description Abstract Background Observational studies have identified a possible connection between lipid-lowering medications and respiratory illnesses. However, it remains unclear whether lipid-lowering drugs is causative for respiratory diseases, and we aimed to answer this question. Methods We performed Mendelian randomization (MR) analyses by integrating data from genome-wide association studies (GWAS). Three statistical approaches were employed for MR analysis: inverse variance weighting (IVW), MR-Egger, and weighted median. The purpose was to evaluate the causal relationships between 10 drug targets that lower lipid levels and the likelihood of developing 7 respiratory diseases. Additional sensitivity analyses were conducted to ensure the robustness and validity of the results. Results After adjusting for multiple testing, our MR analysis identified APOB (odd ratios [OR]: 0.86; 95% confidence interval [CI]: 0.77 to 0.97; PIVW = 0.01) and PCSK9 (OR: 0.84; 95% CI: 0.72 to 0.97; PIVW = 0.02) as significant risk targets for asthma. Additionally, LDLR was found to be a significant risk target for chronic obstructive pulmonary disease (OR: 0.81; 95% CI: 0.67 to 0.98; PIVW = 0.03). The sensitivity analysis validated no proof of heterogeneity or pleiotropy amongst the mentioned results. Conclusions Our findings suggest a likely causal relationship between respiratory diseases and lipid-lowering drug targets. Further mechanistic and clinical research is needed to confirm and validate these findings.
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spelling doaj-art-06d7146867584f9d9bd3f3763401dc422025-08-20T02:48:11ZengBMCBMC Pulmonary Medicine1471-24662025-02-012511910.1186/s12890-025-03527-xLipid-lowering drug targets associated with risk of respiratory disease: a Mendelian randomization studyZhipeng Gong0Dongsheng Wu1Yin Ku2Congyao Zou3Lin Qiu4Xiaohu Hao5Lunxu Liu6Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan UniversityDepartment of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan UniversityDepartment of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan UniversityWest China School of Pharmacy, Sichuan UniversityWest China School of Medicine, Sichuan UniversityDepartment of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan UniversityDepartment of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan UniversityAbstract Background Observational studies have identified a possible connection between lipid-lowering medications and respiratory illnesses. However, it remains unclear whether lipid-lowering drugs is causative for respiratory diseases, and we aimed to answer this question. Methods We performed Mendelian randomization (MR) analyses by integrating data from genome-wide association studies (GWAS). Three statistical approaches were employed for MR analysis: inverse variance weighting (IVW), MR-Egger, and weighted median. The purpose was to evaluate the causal relationships between 10 drug targets that lower lipid levels and the likelihood of developing 7 respiratory diseases. Additional sensitivity analyses were conducted to ensure the robustness and validity of the results. Results After adjusting for multiple testing, our MR analysis identified APOB (odd ratios [OR]: 0.86; 95% confidence interval [CI]: 0.77 to 0.97; PIVW = 0.01) and PCSK9 (OR: 0.84; 95% CI: 0.72 to 0.97; PIVW = 0.02) as significant risk targets for asthma. Additionally, LDLR was found to be a significant risk target for chronic obstructive pulmonary disease (OR: 0.81; 95% CI: 0.67 to 0.98; PIVW = 0.03). The sensitivity analysis validated no proof of heterogeneity or pleiotropy amongst the mentioned results. Conclusions Our findings suggest a likely causal relationship between respiratory diseases and lipid-lowering drug targets. Further mechanistic and clinical research is needed to confirm and validate these findings.https://doi.org/10.1186/s12890-025-03527-xLipid-lowering drug targetRespiratory diseaseMendelian randomization
spellingShingle Zhipeng Gong
Dongsheng Wu
Yin Ku
Congyao Zou
Lin Qiu
Xiaohu Hao
Lunxu Liu
Lipid-lowering drug targets associated with risk of respiratory disease: a Mendelian randomization study
BMC Pulmonary Medicine
Lipid-lowering drug target
Respiratory disease
Mendelian randomization
title Lipid-lowering drug targets associated with risk of respiratory disease: a Mendelian randomization study
title_full Lipid-lowering drug targets associated with risk of respiratory disease: a Mendelian randomization study
title_fullStr Lipid-lowering drug targets associated with risk of respiratory disease: a Mendelian randomization study
title_full_unstemmed Lipid-lowering drug targets associated with risk of respiratory disease: a Mendelian randomization study
title_short Lipid-lowering drug targets associated with risk of respiratory disease: a Mendelian randomization study
title_sort lipid lowering drug targets associated with risk of respiratory disease a mendelian randomization study
topic Lipid-lowering drug target
Respiratory disease
Mendelian randomization
url https://doi.org/10.1186/s12890-025-03527-x
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