Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysisInt COPD Genetics Consortium, Zhu, Z., Wang, X., Li, X., Lin, Y., Shen, S., Liu, C-L., Hobbs, B. D., Hasegawa, K., Liang, L., Boezen, H. M., Camargo, C. A., Cho, M. H. & Christiani, D. C., 2-Apr-2019, In : Respiratory Research. 20, 1, 14 p., 64.
Research output: Contribution to journal › Article › Academic › peer-review
Background: A 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.
Methods: We conducted a large-scale cross-trait genome-wide association study to investigate genetic overlap between COPD (N-case = 12,550, N-control = 46,368) from the International COPD Genetics Consortium and four primary cardiac traits: resting heart rate (RHR) (N = 458,969), high blood pressure (HBP) (N-case = 144,793, N-control = 313,761), coronary artery disease (CAD)(N-case = 60,801, N-control = 123,504), and stroke (N-case = 40,585, N-control = 406,111) from UK Biobank, CARDIoGRAMplusC4D Consortium, and International Stroke Genetics Consortium data.
Results: RHR 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).
Conclusion: In a set of large-scale GWAS, we identify evidence of shared genetics between COPD and cardiac traits.
|Number of pages||14|
|Publication status||Published - 2-Apr-2019|
- Chronic obstructive pulmonary disease, Cardiovascular diseases, Genetic overlap, OXIDATIVE STRESS, ASSOCIATION, LOCI, EXPRESSION, HEART, TRANSCRIPTION, METAANALYSIS, NICOTINE, REPAIR, POWER