New Genes Linked to COPD

[[{"type":"media","view_mode":"media_crop","fid":"57394","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_6363327224171","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7232","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 194px; width: 200px; float: right;","title":"","typeof":"foaf:Image"}}]]A new study has identified 13 new genes linked to COPD, 4 of which have never before been linked to lung function. The study also found areas of the genome in which there was overlap between COPD and two other lung diseases: pulmonary fibrosis or asthma.¹

The study was part of the International COPD Genetics Consortium (ICGC) a multinational collaboration aimed at identifying susceptibility genes for COPD. It represents the largest genome-wide association study (GWAS) of COPD so far. 

"We are excited about these findings because we have not only uncovered new genetic risk factors for COPD, but also shown overlap of COPD genetic risk with the risk for asthma and pulmonary fibrosis," lead author Brian Hobbs, MD, MMSc, of Brigham and Women’s Hospital (Boston, MA) said in a press release. 

"This is the first step in a longer process in which we hope to better understand the genetic basis for COPD, or what may be several different diseases that present as COPD. Now that we know there are new regions of the genome associated with COPD, we can build on this research by probing new biological pathways with the ultimate goal of improving therapies for our patients with this disease," he added.

COPD represents one of the leading cause of death worldwide. Smoking greatly increases the risk for the disease, but genetics also play a role. 

To evaluate the genetic contributions to COPD, researchers did a GWAS in a group of people with European or African ancestry: 15,256 with COPD and 47,936 without COPD.  Then they re-tested the most highly significant results in a second group of patients: 9498 with COPD and 9748 without COPD. Finally, they combined their results using meta-analytic techniques.  Results were adjusted for age, sex, and smoking.

Results:

 â–º Identified 22 genetic loci linked to COPD:

     - 13 had not been previously linked to COPD

     - 4 had not been previously linked to lung function

     - Nine had been previously linked to measures of lung function used in diagnosing COPD (FEV₁, FEV₁/FVC)

     - 2 were shared with pulmonary fibrosis, though the fibrosis allele was associated with decreased risk of COPD

     - 1 was linked to shared susceptibility to asthma and obesity

Results suggest shared heritability with asthma and cigarette smoking (even though the analysis adjusted for smoking). Moreover, most of the genes that were significantly associated with COPD overlapped with lung function. So the results provide support for future studies about variability in lung function and risk for COPD, as well as shared genetic contributions to asthma and COPD, say the authors.

"While it is extremely important that patients not smoke for many health reasons - including the prevention of COPD - we know that smoking cessation may not be enough to stave off the disease. Many patients with COPD experience self-blame, but they may be comforted to know that genetics does play a role in who ultimately develops the disease," senior author Michael Cho, MD, MPH, said in a press release.

Take Home Points

• Largest genome-wide association study to date has identified 13 new genes linked to COPD, 4 of which have never before been linked to lung function

• Two genes were shared with pulmonary fibrosis, though the fibrosis allele was associated with decreased risk of COPD

• One gene was linked to shared susceptibility to asthma and obesity

• The results provide support for future studies about variability in lung function and risk for COPD, as well as shared genetic contributions to asthma and COPD

Source: Hobbs BD, de Jong K, Lamontagne M, et al. Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis. Nat Genet. 2017;49:426-432.