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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.

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Authors
Wain, Louise V
Shrine, Nick
Artigas, María Soler
Erzurumluoglu, A Mesut
Noyvert, Boris
Bossini-Castillo, Lara
Obeidat, Ma'en
Henry, Amanda P
Portelli, Michael A
Hall, Robert J
Billington, Charlotte K
Rimington, Tracy L
Fenech, Anthony G
John, Catherine
Blake, Tineka
Jackson, Victoria E
Allen, Richard J
Prins, Bram P
Campbell, Archie
Porteous, David J
Jarvelin, Marjo-Riitta
Wielscher, Matthias
James, Alan L
Hui, Jennie
Wareham, Nicholas J
Zhao, Jing Hua
Wilson, James F
Joshi, Peter K
Stubbe, Beate
Rawal, Rajesh
Schulz, Holger
Imboden, Medea
Probst-Hensch, Nicole M
Karrasch, Stefan
Gieger, Christian
Deary, Ian J
Harris, Sarah E
Marten, Jonathan
Rudan, Igor
Enroth, Stefan
Gyllensten, Ulf
Kerr, Shona M
Polasek, Ozren
Kähönen, Mika
Surakka, Ida
Vitart, Veronique
Hayward, Caroline
Lehtimäki, Terho
Raitakari, Olli T
Evans, David M
Henderson, A John
Pennell, Craig E
Wang, Carol A
Sly, Peter D
Wan, Emily S
Busch, Robert
Hobbs, Brian D
Litonjua, Augusto A
Sparrow, David W
Gulsvik, Amund
Bakke, Per S
Crapo, James D
Beaty, Terri H
Hansel, Nadia N
Mathias, Rasika A
Ruczinski, Ingo
Barnes, Kathleen C
Bossé, Yohan
Joubert, Philippe
van den Berge, Maarten
Brandsma, Corry-Anke
Paré, Peter D
Sin, Don D
Nickle, David C
Hao, Ke
Gottesman, Omri
Dewey, Frederick E
Bruse, Shannon E
Carey, David J
Kirchner, H Lester
Jonsson, Stefan
Thorleifsson, Gudmar
Jonsdottir, Ingileif
Gislason, Thorarinn
Stefansson, Kari
Schurmann, Claudia
Nadkarni, Girish
Bottinger, Erwin P
Loos, Ruth J F
Walters, Robin G
Chen, Zhengming
Millwood, Iona Y
Vaucher, Julien
Kurmi, Om P
Li, Liming
Hansell, Anna L
Brightling, Chris
Zeggini, Eleftheria
Cho, Michael H
Silverman, Edwin K
Sayers, Ian
Trynka, Gosia
Morris, Andrew P
Strachan, David P
Hall, Ian P
Tobin, Martin D
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Issue Date
2017-03

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Citation
Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets. 2017, 49 (3):416-425 Nat. Genet.
Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
Additional Links
http://www.nature.com/ng/journal/v49/n3/pdf/ng.3787.pdf
Rights
Archived with thanks to Nature genetics
ae974a485f413a2113503eed53cd6c53
10.1038/ng.3787
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English Journal Articles (Peer Reviewed)

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