Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

, , Understanding Society Scientific Group, Phuwanat Sakornsakolpat, Dmitry Prokopenko, Maxime Lamontagne, Nicola F. Reeve, Anna L. Guyatt, Victoria E. Jackson, Nick Shrine, Dandi Qiao, Traci M. Bartz, Deog Kyeom Kim, Mi Kyeong Lee, Jeanne C. Latourelle, Xingnan Li, Jarrett D. Morrow, Ma’en Obeidat, Annah B. Wyss, Per BakkeR. Graham Barr, Terri H. Beaty, Steven A. Belinsky, Guy G. Brusselle, James D. Crapo, Kim de Jong, Dawn L. DeMeo, Tasha E. Fingerlin, Sina A. Gharib, Amund Gulsvik, Ian P. Hall, John E. Hokanson, Woo Jin Kim, David A. Lomas, Stephanie J. London, Deborah A. Meyers, George T. O’Connor, Stephen I. Rennard, David A. Schwartz, Pawel Sliwinski, David Sparrow, David P. Strachan, Ruth Tal-Singer, Yohannes Tesfaigzi, Jørgen Vestbo, Judith M. Vonk, Jae Joon Yim, Xiaobo Zhou, Yohan Bossé, Ani Manichaikul, Lies Lahousse, Edwin K. Silverman, H. Marike Boezen, Louise V. Wain, Martin D. Tobin, Brian D. Hobbs, Michael H. Cho (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

193 Citations (Scopus)


Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10 −8 ; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.

Original languageEnglish
Pages (from-to)494-505
Number of pages12
JournalNature Genetics
Issue number3
Publication statusPublished - 1 Mar 2019


  • Adult
  • Aged
  • Asthma/genetics
  • Case-Control Studies
  • Female
  • Gene Expression/genetics
  • Genetic Loci/genetics
  • Genetic Predisposition to Disease/genetics
  • Genome-Wide Association Study/methods
  • Humans
  • Lung/physiopathology
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide/genetics
  • Pulmonary Disease, Chronic Obstructive/genetics
  • Pulmonary Fibrosis/genetics
  • Smoking/genetics

ASJC Scopus subject areas

  • Genetics


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