@article{ce960b3fcbea47ef9eafa52ed737112b,
title = "Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations",
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 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. ",
author = "{SpiroMeta consortium} and {International COPD Genetics Consortium} and {Understanding Society Scientific Group} and Phuwanat Sakornsakolpat and Dmitry Prokopenko and Maxime Lamontagne and Reeve, {Nicola F.} and Guyatt, {Anna L.} and Jackson, {Victoria E.} and Nick Shrine and Dandi Qiao and Bartz, {Traci M.} and Kim, {Deog Kyeom} and Lee, {Mi Kyeong} and Latourelle, {Jeanne C.} and Xingnan Li and Morrow, {Jarrett D.} and Ma{\textquoteright}en Obeidat and Wyss, {Annah B.} and Per Bakke and Barr, {R. Graham} and Beaty, {Terri H.} and Belinsky, {Steven A.} and Brusselle, {Guy G.} and Crapo, {James D.} and {de Jong}, Kim and DeMeo, {Dawn L.} and Fingerlin, {Tasha E.} and Gharib, {Sina A.} and Amund Gulsvik and Hall, {Ian P.} and Hokanson, {John E.} and Kim, {Woo Jin} and Lomas, {David A.} and London, {Stephanie J.} and Meyers, {Deborah A.} and O{\textquoteright}Connor, {George T.} and Rennard, {Stephen I.} and Schwartz, {David A.} and Pawel Sliwinski and David Sparrow and Strachan, {David P.} and Ruth Tal-Singer and Yohannes Tesfaigzi and J{\o}rgen Vestbo and Vonk, {Judith M.} and Yim, {Jae Joon} and Xiaobo Zhou and Yohan Boss{\'e} and Ani Manichaikul and Lies Lahousse and Silverman, {Edwin K.} and Boezen, {H. Marike} and Wain, {Louise V.} and Tobin, {Martin D.} and Hobbs, {Brian D.} and Cho, {Michael H.} and Nick Shrine and Guyatt, {Anna L.} and Chiara Batini and Zhao, {Jing Hua} and Matthias Wielscher and Stefan Weiss and Kentistou, {Katherine A.} and Cook, {James P.} and Jennie Hui and Stefan Karrasch and Medea Imboden and Harris, {Sarah E.} and Jonathan Marten and Stefan Enroth and Kerr, {Shona M.} and Ida Surakka and Veronique Vitart and Terho Lehtim{\"a}ki and Ralf Ewert and Christian Gieger and Georg Homuth and Joshi, {Peter K.} and Claudia Langenberg and Lars Lind and Jian{\textquoteright}an Luan and Anubha Mahajan and Alison Murray and Porteous, {David J.} and Rajesh Rawal and Smith, {Blair H.} and Timmers, {Paul R.H.J.} and Raitakari, {Olli T.} and Mika K{\"a}h{\"o}nen and Ozren Polasek and Ulf Gyllensten and Igor Rudan and Deary, {Ian J.} and Probst-Hensch, {Nicole M.} and Holger Schulz and James, {Alan L.} and Wilson, {James F.} and Beate Stubbe and Eleftheria Zeggini and Jarvelin, {Marjo Riitta} and Nick Wareham and Caroline Hayward and Morris, {Andrew P.} and Strachan, {David P.} and Hall, {Ian P.} and Tobin, {Martin D.} and Wain, {Louise V.} and Alvar Agusti and Wayne Anderson and Nawar Bakerly and Per Bakke and Robert Bals and Barnes, {Kathleen C.} and Barr, {R. Graham} and Beaty, {Terri H.} and Bleecker, {Eugene R.} and Boezen, {H. Marike} and Yohan Boss{\'e} and Russell Bowler and Christopher Brightling and {de Bruijne}, Marleen and Castaldi, {Peter J.} and Bartolome Celli and Cho, {Michael H.} and Coxson, {Harvey O.} and Crapo, {James D.} and Ron Crystal and {de Jong}, Pim and Asger Dirksen and Jennifer Dy and Marilyn Foreman and Judith Garcia-Aymerich and Pierre Gevenois and Soumitra Ghosh and Hester Gietema and Amund Gulsvik and Hall, {Ian P.} and Nadia Hansel and Hersh, {Craig P.} and Hobbs, {Brian D.} and Eric Hoffman and Noor Kalsheker and Kauczor, {Hans Ulrich} and Kim, {Woo Jin} and Kim, {Deog Kyeom} and Tarja Laitinen and Diether Lambrechts and Lee, {Sang Do} and Litonjua, {Augusto A.} and Lomas, {David A.} and London, {Stephanie J.} and Loth, {Daan W.} and Lutz, {Sharon M.} and David Lynch and William MacNee and McDonald, {Merry Lynn} and Meyers, {Deborah A.} and Newell, {John D.} and Nordestgaard, {Borge G.} and O{\textquoteright}Connor, {George T.} and Ma{\textquoteright}en Obeidat and Oh, {Yeon Mok} and Par{\'e}, {Peter D.} and Massimo Pistolesi and Postma, {Dirkje S.} and Milo Puhan and Elizabeth Regan and Rich, {Stephen S.} and Seo, {Joon Beom} and Andrea Short and Silverman, {Edwin K.} and David Sparrow and Berend Stoel and Strachan, {David P.} and Nicola Sverzellati and Ruth Tal-Singer and {ter Riet}, Gerben and Yohannes Tesfaigzi and Tobin, {Martin D.} and {Van Beek}, {Edwin J.R.} and {van Ginneken}, Bram and J{\o}rgen Vestbo and Vogelmeier, {Claus F.} and Wain, {Louise V.} and Adam Wanner and George Washko and Els Wauters and Wouters, {Emiel F.M.} and Young, {Robert P.} and Loems Zeigler-Heitbrock",
year = "2019",
month = feb,
day = "25",
doi = "10.1038/s41588-018-0342-2",
language = "English",
volume = "51",
pages = "494--505",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group - Macmillan Publishers",
number = "3",
}