Journal article

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

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 Bakke, R Graham Barr, Terri H Beaty, Steven A Belinsky Show all

NATURE GENETICS | NATURE PUBLISHING GROUP | Published : 2019

Abstract

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 ..

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University of Melbourne Researchers

Grants

Awarded by NHLBI


Awarded by Parker B. Francis Research Opportunity Award



Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES


Funding Acknowledgements

This work was supported by the Prince Mahidol Award Youth Program Scholarship (P. Sakornsakolpat); NHLBI R01HL084323, R01HL113264, R01HL089856, and P01HL105339 (E.K.S.); K08HL136928 (B.D.H.), the Parker B. Francis Research Opportunity Award (B.D.H.); and R01HL113264, R01HL137927, P01HL105339, and P01HL132825 (M.H.C.). This research was conducted by using the UK Biobank resource under application numbers 20915 (M.H.C.) and 648 (M.D.T.). Please refer to the Supplementary Note for full acknowledgements. Funding bodies had no role in the design of the study, the collection, analysis, or interpretation of the data, or the writing of the manuscript.