| Title: | Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis |
| Journal: | Respiratory Research |
| Published: | 2 Apr 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30940143/ |
| DOI: | https://doi.org/10.1186/s12931-019-1036-8 |
| URL: | https://respiratory-research.biomedcentral.com/track/pdf/10.1186/s12931-019-1036-8 |
Publication 7663
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Abstract
BackgroundA growing number of studies clearly demonstrate a substantial association between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD), although little is known about the shared genetics that contribute to this association.MethodsWe conducted a large-scale cross-trait genome-wide association study to investigate genetic overlap between COPD (Ncase = 12,550, Ncontrol = 46,368) from the International COPD Genetics Consortium and four primary cardiac traits: resting heart rate (RHR) (N = 458,969), high blood pressure (HBP) (Ncase = 144,793, Ncontrol = 313,761), coronary artery disease (CAD)(Ncase = 60,801, Ncontrol = 123,504), and stroke (Ncase = 40,585, Ncontrol = 406,111) from UK Biobank, CARDIoGRAMplusC4D Consortium, and International Stroke Genetics Consortium data.ResultsRHR and HBP had modest genetic correlation, and CAD had borderline evidence with COPD at a genome-wide level. We found evidence of local genetic correlation with particular regions of the genome. Cross-trait meta-analysis of COPD identified 21 loci jointly associated with RHR, 22 loci with HBP, and 3 loci with CAD. Functional analysis revealed that shared genes were enriched in smoking-related pathways and in cardiovascular, nervous, and immune system tissues. An examination of smoking-related genetic variants identified SNPs located in 15q25.1 region associated with cigarettes per day, with effects on RHR and CAD. A Mendelian randomization analysis showed a significant positive causal effect of COPD on RHR (causal estimate = 0.1374, P = 0.008).ConclusionIn a set of large-scale GWAS, we identify evidence of shared genetics between COPD and cardiac traits.13 Authors
- Zhaozhong Zhu
- Xiaofang Wang
- Xihao Li
- Yifei Lin
- Sipeng Shen
- Cong-Lin Liu
- Brain D. Hobbs
- Kohei Hasegawa
- Liming Liang
- H. Marike Boezen
- Carlos A. Camargo
- Michael H. Cho
- David C. Christiani
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