scholarly journals Expression of long non‐coding RNA LUCAT1 in patients with chronic obstructive pulmonary disease and its potential functions in regulating cigarette smoke extract‐induced 16HBE cell proliferation and apoptosis

2021 ◽  
Author(s):  
Shan Zhao ◽  
Chunyan Lin ◽  
Tao Yang ◽  
Xiaoyu Qian ◽  
Junjie Lu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cell Proliferation ◽  
Pulmonary Disease ◽  
Cigarette Smoke Extract ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Non Coding Rna ◽  
Proliferation And Apoptosis ◽  
16Hbe Cell ◽  
Long Non Coding Rna

scholarly journals A Systematic Analysis of Protein-altering Exonic Variants in Chronic Obstructive Pulmonary Disease

2021 ◽  
Author(s):  
Matthew Moll ◽  
Victoria E. Jackson ◽  
Bing Yu ◽  
Megan L. Grove ◽  
Stephanie J. London ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cell Proliferation ◽  
Pulmonary Disease ◽  
Association Studies ◽  
Meta Analysis ◽  
Effect Sizes ◽  
Chronic Obstructive ◽  
Genome Wide Association Studies ◽  
Obstructive Pulmonary Disease ◽  
Coding Variants

Genome-wide association studies (GWASs) have identified regions associated with chronic obstructive pulmonary disease (COPD). GWASs of other diseases have shown an approximately 10-fold overrepresentation of nonsynonymous variants, despite limited exonic coverage on genotyping arrays. We hypothesized that a large-scale analysis of coding variants could discover novel genetic associations with COPD, including rare variants with large effect sizes. We performed a meta-analysis of exome arrays from 218,399 controls and 33,851 moderate-to-severe COPD cases. All exome-wide significant associations were present in regions previously identified by GWAS. We did not identify any novel rare coding variants with large effect sizes. Within GWAS regions on chromosomes 5q, 6p, and 15q, four coding variants were conditionally significant (p < 0.00015) when adjusting for lead GWAS SNPs. A common GSDMB splice variant (rs11078928) previously associated with decreased risk for asthma, was nominally associated with decreased risk for COPD (MAF = 0.46, p=1.8e-4). Two stop variants in CCHCR1, a gene involved in regulating cell proliferation, were associated with COPD (both p < 0.0001). The SERPINA1 Z allele was associated with a random effects odds ratio of 1.43 for COPD (95% CI: 1.17-1.74), though with marked heterogeneity across studies. Overall, COPD-associated exonic variants were identified in genes involved in DNA methylation, cell-matrix interactions, cell proliferation, and cell death. In conclusion, we performed the largest exome array meta-analysis of COPD to date and identified potential functional coding variants. Future studies are needed to identify rarer variants, and further define the role of coding variants in COPD pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document