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PMID: 30940143 Published · epublish English Journal Article

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

Respiratory research ·Vol. 20 ·No. 1 ·2019-04-02 ·Pages 64

Zhu Z, Wang X, Li X, Lin Y, Shen S, Liu CL, Hobbs BD, Hasegawa K, Liang L, International COPD Genetics Consortium, Boezen HM, Camargo CA, Cho MH, Christiani DC

Abstract

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. We 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. 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). In a set of large-scale GWAS, we identify evidence of shared genetics between COPD and cardiac traits.

Keywords
Cardiovascular diseases Chronic obstructive pulmonary disease Genetic overlap
MeSH Terms
Cardiovascular Diseases/diagnosis,epidemiology,genetics Databases, Genetic/trends Genetic Predisposition to Disease/epidemiology,genetics Genetic Variation/genetics Genome-Wide Association Study/methods Humans Polymorphism, Single Nucleotide/genetics Pulmonary Disease, Chronic Obstructive/diagnosis,epidemiology,genetics Quantitative Trait, Heritable
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Zhu Zhaozhong
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. | Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Wang Xiaofang
Department of Cardiology, First Affiliated Hospital, College of Medicine, Zhengzhou University, Zhengzhou, China.
Li Xihao
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Lin Yifei
Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Shen Sipeng
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Liu Cong-Lin
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Hobbs Brain D
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Hasegawa Kohei
Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Liang Liming
Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. | Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
International COPD Genetics Consortium
Boezen H Marike
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. | Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Camargo Carlos A
Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA. | Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Cho Michael H
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. | Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Christiani David C
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. [email protected]. | Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. [email protected].
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Article Info
Journal
Respiratory research
Abbr.
Respir Res
ISSN
1465-993X
DOI
10.1186/s12931-019-1036-8
Email
[email protected]
Published
2019-04-02
Epub
2019-00-02
Pages
64
Language
English
Region
England
NLM ID
101090633
PMCID
PMC6444755
Grants
NHLBI NIH HHS · R01 HL113264 · United States
National Heart, Lung, and Blood Institute · R01HL113264
National Institute of Environmental Health Sciences · P30ES000002
National Heart, Lung, and Blood Institute · R01HL060710
NHLBI NIH HHS · K08 HL136928 · United States
External Links
PubMed source DOI: 10.1186/s12931-019-1036-8 PMC Full Text View journal details
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