Format

Send to

Choose Destination
Respir Res. 2019 Apr 2;20(1):64. doi: 10.1186/s12931-019-1036-8.

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

Author information

1
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
2
Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
3
Department of Cardiology, First Affiliated Hospital, College of Medicine, Zhengzhou University, Zhengzhou, China.
4
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
5
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
6
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
7
Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
8
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
9
Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
10
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
11
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. dchris@hsph.harvard.edu.
12
Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. dchris@hsph.harvard.edu.

Abstract

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 (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.

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.

KEYWORDS:

Cardiovascular diseases; Chronic obstructive pulmonary disease; Genetic overlap

PMID:
30940143
PMCID:
PMC6444755
DOI:
10.1186/s12931-019-1036-8
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center