Author:
Sakornsakolpat Phuwanat,Prokopenko Dmitry,Lamontagne Maxime,Reeve Nicola F.,Guyatt Anna L.,Jackson Victoria E.,Shrine Nick,Qiao Dandi,Bartz Traci M.,Kim Deog Kyeom,Lee Mi Kyeong,Latourelle Jeanne C.,Li Xingnan,Morrow Jarrett D.,Obeidat Ma’en,Wyss Annah B.,Zhou Xiaobo,Bakke Per,Barr R Graham,Beaty Terri H.,Belinsky Steven A.,Brusselle Guy G.,Crapo James D.,Jong Kim de,DeMeo Dawn L.,Fingerlin Tasha E.,Gharib Sina A.,Gulsvik Amund,Hall Ian P.,Hokanson John E.,Kim Woo Jin,Lomas David A.,London Stephanie J.,Meyers Deborah A.,O’Connor George T.,Rennard Stephen I.,Schwartz David A.,Sliwinski Pawel,Sparrow David,Strachan David P.,Tal-Singer Ruth,Tesfaigzi Yohannes,Vestbo Jørgen,Vonk Judith M.,Yim Jae-Joon,Bossé Yohan,Manichaikul Ani,Lahousse Lies,Silverman Edwin K.,Boezen H. Marike,Wain Louise V.,Tobin Martin D.,Hobbs Brian D.,Cho Michael H.,
Abstract
SummaryChronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide novel insights into disease pathogenesis. To broaden COPD genetic risk loci discovery and identify cell type and phenotype associations 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 with P value < 5×10−8; 47 were previously described in association with either COPD or population-based lung function. Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and alveolar type II cells. We found 9 shared genomic regions between COPD and asthma and 5 between COPD and pulmonary fibrosis. COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations. Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD.
Publisher
Cold Spring Harbor Laboratory