The COPD genetic association compendium: a comprehensive online database of COPD genetic associations

Abstract

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. COPD is thought to arise from the interaction of environmental exposures and genetic susceptibility, and major research efforts are underway to identify genetic determinants of COPD susceptibility. With the exception of SERPINA1, genetic associations with COPD identified by candidate gene studies have been inconsistently replicated, and this literature is difficult to interpret. We conducted a systematic review and meta-analysis of all population-based, case-control candidate gene COPD studies indexed in PubMed before 16 July 2008. We stored our findings in an online database, which serves as an up-to-date compendium of COPD genetic associations and cumulative meta-analysis estimates. On the basis of our systematic review, the vast majority of COPD candidate gene era studies are underpowered to detect genetic effect odds ratios of 1.2-1.5. We identified 27 genetic variants with adequate data for quantitative meta-analysis. Of these variants, four were significantly associated with COPD susceptibility in random effects meta-analysis, the GSTM1 null variant (OR 1.45, CI 1.09-1.92), rs1800470 in TGFB1 (0.73, CI 0.64-0.83), rs1800629 in TNF (OR 1.19, CI 1.01-1.40) and rs1799896 in SOD3 (OR 1.97, CI 1.24-3.13). In summary, most COPD candidate gene era studies are underpowered to detect moderate-sized genetic effects. Quantitative meta-analysis identified four variants in GSTM1, TGFB1, TNF and SOD3 that show statistically significant evidence of association with COPD susceptibility.

A Genome-Wide Association Study In COPD Identifies A Susceptibility Locus On Chromosome 19q13

“…Numerous studies have demonstrated a genetic component to COPD and smoking-related changes in lung function (5 -8). However, the results of many small candidate gene studies have been inconsistent (9,10). Genomewide association studies (GWASs) of COPD (11)(12)(13) have, to date, identified three susceptibility loci that have been well replicated (14)(15)(16)(17)(18)(19)(20)(21).…”

Combined Analysis of EPHX1, GSTP1, GSTM1 and GSTT1 Gene Polymorphisms in Relation to Chronic Obstructive Pulmonary Disease Risk and Lung Function Impairment

“…The GSTP1 105Ile/Val substitution is located near the substrate-binding site, leading to a different enzyme activity depending on the type of chemical reaction [18]. These GST polymorphisms have been investigated in relation to COPD, but without definitive conclusions [19][20][21][22][23][24][25][26].…”

Chronic Obstructive Pulmonary Disease Genetics: A Review of the Past and a Look Into the Future

“…18 In a similar meta-analysis, Castaldi and colleagues examined all candidate gene studies in COPD performed up to 2009. 19 The definition of COPD varied significantly in many studies, from strict spirometric definitions to physician diagnoses. They were able to identify 27 variants that were studied in 3 or more independent populations.…”