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Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis

Int 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 journalArticleAcademicpeer-review

  • Int COPD Genetics Consortium
  • 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

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.

Original languageEnglish
Article number64
Number of pages14
JournalRespiratory Research
Volume20
Issue number1
Publication statusPublished - 2-Apr-2019

    Keywords

  • Chronic obstructive pulmonary disease, Cardiovascular diseases, Genetic overlap, OXIDATIVE STRESS, ASSOCIATION, LOCI, EXPRESSION, HEART, TRANSCRIPTION, METAANALYSIS, NICOTINE, REPAIR, POWER

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