title: The association of genome-wide significant spirometric loci with chronic obstructive pulmonary disease susceptibility.
abstract: Two recent metaanalyses of genome-wide association studies conducted by the CHARGE and SpiroMeta consortia identified novel loci yielding evidence of association at or near genome-wide significance (GWS) with FEV(1) and FEV(1)/FVC. We hypothesized that a subset of these markers would also be associated with chronic obstructive pulmonary disease (COPD) susceptibility. Thirty-two single-nucleotide polymorphisms (SNPs) in or near 17 genes in 11 previously identified GWS spirometric genomic regions were tested for association with COPD status in four COPD case-control study samples (NETT/NAS, the Norway case-control study, ECLIPSE, and the first 1,000 subjects in COPDGene; total sample size, 3,456 cases and 1,906 controls). In addition to testing the 32 spirometric GWS SNPs, we tested a dense panel of imputed HapMap2 SNP markers from the 17 genes located near the 32 GWS SNPs and in a set of 21 well studied COPD candidate genes. Of the previously identified GWS spirometric genomic regions, three loci harbored SNPs associated with COPD susceptibility at a 5% false discovery rate: the 4q24 locus including FLJ20184/INTS12/GSTCD/NPNT, the 6p21 locus including AGER and PPT2, and the 5q33 locus including ADAM19. In conclusion, markers previously associated at or near GWS with spirometric measures were tested for association with COPD status in data from four COPD case-control studies, and three loci showed evidence of association with COPD susceptibility at a 5% false discovery rate.
authors.affiliation: Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts, USA. peter.castaldi@channing.harvard.edu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Castaldi
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cho
authors.forename: Augusto A
authors.initials: AA
authors.lastname: Litonjua
authors.forename: Per
authors.initials: P
authors.lastname: Bakke
authors.forename: Amund
authors.initials: A
authors.lastname: Gulsvik
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Wayne
authors.initials: W
authors.lastname: Anderson
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.forename: Nan
authors.initials: N
authors.lastname: Laird
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*
chemical_list: D005819:Genetic Markers