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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.

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