title: 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.
authors.affiliation: Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Castaldi
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cho
authors.forename: Matthew
authors.initials: M
authors.lastname: Cohn
authors.forename: Fawn
authors.initials: F
authors.lastname: Langerman
authors.forename: Sienna
authors.initials: S
authors.lastname: Moran
authors.forename: Nestor
authors.initials: N
authors.lastname: Tarragona
authors.forename: Hala
authors.initials: H
authors.lastname: Moukhachen
authors.forename: Radhika
authors.initials: R
authors.lastname: Venugopal
authors.forename: Delvina
authors.initials: D
authors.lastname: Hasimja
authors.forename: Esther
authors.initials: E
authors.lastname: Kao
authors.forename: Byron
authors.initials: B
authors.lastname: Wallace
authors.forename: Craig P
authors.initials: CP
authors.lastname: Hersh
authors.forename: Sachin
authors.initials: S
authors.lastname: Bagade
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Trikalinos
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D030541:Databases, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009862:Online Systems; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D005982:Glutathione Transferase; D013482:Superoxide Dismutase; D053773:Transforming Growth Factor beta1; C508960:TGFB1 protein, human; C441642:SOD3 protein, human