115563
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.6 Breast Cancer (Dove Med Press)
- 4.3 Clin Epidemiol
- 2.6 Cancer Manag Res
- 3.2 Infect Drug Resist
- 4.1 Clin Interv Aging
- 6.1 Drug Des Dev Ther
- 4.1 Int J Chronic Obstr
- 8.7 Int J Nanomed
- 2.5 Int J Women's Health
- 3.2 Neuropsych Dis Treat
- 2.4 OncoTargets Ther
- 2.6 Patient Prefer Adher
- 2.6 Ther Clin Risk Manag
- 3.1 J Pain Res
- 3.5 Diabet Metab Synd Ob
- 4.5 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 2.4 Pharmgenomics Pers Med
- 2.6 Risk Manag Healthc Policy
- 4.6 J Inflamm Res
- 2.3 Int J Gen Med
- 3.9 J Hepatocell Carcinoma
- 3.3 J Asthma Allergy
- 2.5 Clin Cosmet Investig Dermatol
- 3.0 J Multidiscip Healthc
已发表论文
慢性阻塞性肺疾病与心血管疾病共病的遗传结构：探索共同机制及潜在治疗靶点
Received 7 October 2025
Accepted for publication 18 December 2025
Published 8 January 2026 Volume 2026:21 572586
DOI https://doi.org/10.2147/COPD.S572586
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Jill Ohar
Shiyu Chen,1,* Xiaojian Li,1,* Rongfang Xie1,2
1Clinical Medical College,Jiangxi University of Chinese Medicine, Nanchang, 330004, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, 330006, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Rongfang Xie, Clinical Medical College, Jiangxi University of Chinese Medicine, Nanchang, 330004, People’s Republic of China, Email 283700257@qq.com
Background: Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs), including hypertension (HTN), coronary heart disease (CHD), and heart failure (HF), are major global health burdens. The shared genetic mechanisms underlying the high comorbidity between COPD and CVDs remain unclear.
Methods: We integrated large-scale GWAS summary statistics for COPD and three major CVDs (HTN, CHD, HF). Several analytic approaches were applied, including linkage disequilibrium score regression (LDSC), high-definition likelihood (HDL), multi-marker analysis of genomic annotation (MAGMA), pleiotropic analysis under composite null hypothesis (PLACO), and summary-data-based Mendelian randomization (SMR). These methods were used to evaluate genetic correlations, identify shared risk loci, and prioritize potential therapeutic targets.
Results: LDSC and HDL analyses revealed significant positive genetic correlations between COPD and the three CVDs (rg = 0.23– 0.38, P < 0.05). MAGMA enrichment analysis identified 277 unique pleiotropic genes enriched in pathways such as Notch signaling and nicotinic acetylcholine receptor signaling. Tissue-specific analyses indicated that shared genetic signals were enriched not only in the lung and heart but also in neuroendocrine-related tissues such as the cerebellum and pituitary, suggesting the involvement of a potential “lung–heart–brain” multi-organ axis. PLACO identified 94 pleiotropic SNPs, with consistent colocalization signals at 15q25.1 (CHRNA3/5, IREB2) and 4q22 (SOX7). SMR analysis further prioritized 626 candidate genes, including ZNF652, XRCC3, SLC22A5, and SOX7, which may serve as potential therapeutic targets.
Conclusion: This study provides genetic evidence for shared mechanisms linking COPD with HTN, CHD, and HF. It highlights the roles of neurotransmitter receptors, iron metabolism, vascular development, and energy metabolism in COPD–CVD comorbidity. These findings offer insights into precision prevention and therapeutic strategies targeting COPD–CVD comorbidity.
Keywords: chronic obstructive pulmonary disease, hypertension, coronary heart disease, heart failure, GWAS, pleiotropy, drug targets
1Clinical Medical College,Jiangxi University of Chinese Medicine, Nanchang, 330004, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, 330006, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Rongfang Xie, Clinical Medical College, Jiangxi University of Chinese Medicine, Nanchang, 330004, People’s Republic of China, Email 283700257@qq.com
Background: Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs), including hypertension (HTN), coronary heart disease (CHD), and heart failure (HF), are major global health burdens. The shared genetic mechanisms underlying the high comorbidity between COPD and CVDs remain unclear.
Methods: We integrated large-scale GWAS summary statistics for COPD and three major CVDs (HTN, CHD, HF). Several analytic approaches were applied, including linkage disequilibrium score regression (LDSC), high-definition likelihood (HDL), multi-marker analysis of genomic annotation (MAGMA), pleiotropic analysis under composite null hypothesis (PLACO), and summary-data-based Mendelian randomization (SMR). These methods were used to evaluate genetic correlations, identify shared risk loci, and prioritize potential therapeutic targets.
Results: LDSC and HDL analyses revealed significant positive genetic correlations between COPD and the three CVDs (rg = 0.23– 0.38, P < 0.05). MAGMA enrichment analysis identified 277 unique pleiotropic genes enriched in pathways such as Notch signaling and nicotinic acetylcholine receptor signaling. Tissue-specific analyses indicated that shared genetic signals were enriched not only in the lung and heart but also in neuroendocrine-related tissues such as the cerebellum and pituitary, suggesting the involvement of a potential “lung–heart–brain” multi-organ axis. PLACO identified 94 pleiotropic SNPs, with consistent colocalization signals at 15q25.1 (CHRNA3/5, IREB2) and 4q22 (SOX7). SMR analysis further prioritized 626 candidate genes, including ZNF652, XRCC3, SLC22A5, and SOX7, which may serve as potential therapeutic targets.
Conclusion: This study provides genetic evidence for shared mechanisms linking COPD with HTN, CHD, and HF. It highlights the roles of neurotransmitter receptors, iron metabolism, vascular development, and energy metabolism in COPD–CVD comorbidity. These findings offer insights into precision prevention and therapeutic strategies targeting COPD–CVD comorbidity.
Keywords: chronic obstructive pulmonary disease, hypertension, coronary heart disease, heart failure, GWAS, pleiotropy, drug targets