The association of genome-wide significant spirometric loci with chronic obstructive pulmonary disease susceptibility

Peter J. Castaldi, Michael H. Cho, Augusto A. Litonjua, Per Bakke, Amund Gulsvik, David A. Lomas, Wayne Anderson, Terri H. Beaty, John E. Hokanson, James D. Crapo, Nan Laird, Edwin K. Silverman

Research output: Contribution to journalArticle

Abstract

Two recent metaanalyses of genome-wide association studies conducted by the CHARGE and SpiroMeta consortia identified novel loci yielding evidence of associationat or neargenome-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 GWSSNPs and in a set of 21 well studiedCOPDcandidate 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 nearGWSwith 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.

Original languageEnglish (US)
Pages (from-to)1147-1153
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume45
Issue number6
DOIs
StatePublished - Dec 1 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Castaldi, P. J., Cho, M. H., Litonjua, A. A., Bakke, P., Gulsvik, A., Lomas, D. A., Anderson, W., Beaty, T. H., Hokanson, J. E., Crapo, J. D., Laird, N., & Silverman, E. K. (2011). The association of genome-wide significant spirometric loci with chronic obstructive pulmonary disease susceptibility. American journal of respiratory cell and molecular biology, 45(6), 1147-1153. https://doi.org/10.1165/rcmb.2011-0055OC