Back to Search Start Over

Expanded genetic landscape of chronic obstructive pulmonary disease reveals heterogeneous cell type and phenotype associations

Authors :
Maxime Lamontagne
Amund Gulsvik
David A. Lomas
Ian P. Hall
Judith M. Vonk
Kim de Jong
Phuwanat Sakornsakolpat
Sina A. Gharib
Jarrett D. Morrow
George T. O'Connor
Louise V. Wain
Brian D. Hobbs
David A. Schwartz
Steven A. Belinsky
Xingnan Li
Edwin K. Silverman
Anna L. Guyatt
David Sparrow
R. Graham Barr
Ani Manichaikul
Deog Kyeom Kim
John E. Hokanson
Yohannes Tesfaigzi
Martin D. Tobin
James D. Crapo
Victoria E. Jackson
Jørgen Vestbo
Pawel Sliwinski
Xiaobo Zhou
Michael H. Cho
Stephen I. Rennard
Ma'en Obeidat
Dawn L. DeMeo
Mi Kyeong Lee
Stephanie J. London
Terri H. Beaty
H. Marike Boezen
Guy Brusselle
Nick Shrine
Annah B. Wyss
Jeanne C. Latourelle
Traci M. Bartz
Nicola F. Reeve
Woo Jin Kim
Ruth Tal-Singer
Lies Lahousse
Dandi Qiao
Tasha E. Fingerlin
Yohan Bossé
Per Bakke
Dmitry Prokopenko
Jae-Joon Yim
David P. Strachan
Deborah A. Meyers
Publication Year :
2018
Publisher :
Cold Spring Harbor Laboratory, 2018.

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.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....e8cc7766d1bffecf1c0a9c885d3db119
Full Text :
https://doi.org/10.1101/355644