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

Autor: Stefan Enroth, Robert J. Hall, James D. Crapo, Frederick E. Dewey, Victoria E. Jackson, Eleftheria Zeggini, Gudmar Thorleifsson, Terho Lehtimäki, David J. Porteous, Nicole Probst-Hensch, Ian J. Deary, A. Mesut Erzurumluoglu, Bram P. Prins, Maarten van den Berge, Craig E. Pennell, Catherine John, Terri H. Beaty, Claudia Schurmann, Michael H. Cho, Veronique Vitart, Erwin P. Bottinger, Carol A. Wang, H. Lester Kirchner, Medea Imboden, David J. Carey, Archie Campbell, Kari Stefansson, Matthias Wielscher, Ida Surakka, Igor Rudan, Shona M. Kerr, Holger Schulz, Michael A. Portelli, Thorarinn Gislason, Peter D. Paré, James F. Wilson, Boris Noyvert, Beate Stubbe, Zhengming Chen, Ruth J. F. Loos, Ma'en Obeidat, María Soler Artigas, Philippe Joubert, Kathleen C. Barnes, Christian Gieger, Andrew P. Morris, Rajesh Rawal, Yohan Bossé, Peter K. Joshi, Nadia N. Hansel, Emily S. Wan, David M. Evans, David C. Nickle, Caroline Hayward, Stefan Karrasch, Ke Hao, Tracy L. Rimington, Don D. Sin, Alan James, Stefan Jonsson, Shannon Bruse, Amanda P. Henry, Iona Y Millwood, Lara Bossini-Castillo, Ian P. Hall, David Sparrow, Ulf Gyllensten, Ian Sayers, Edwin K. Silverman, Robert Busch, David P. Strachan, Martin D. Tobin, Nick Shrine, Louise V. Wain, Robin G. Walters, Ingileif Jonsdottir, Peter D. Sly, Liming Li, Charlotte K. Billington, Anna Hansell, Omri Gottesman, Om P Kurmi, Ingo Ruczinski, Nicholas J. Wareham, Amund Gulsvik, Per Bakke, Jennie Hui, Corry-Anke Brandsma, Gosia Trynka, Anthony G. Fenech, Brian D. Hobbs, A. John Henderson, Jonathan Marten, Olli T. Raitakari, Richard J. Allen, Augusto A. Litonjua, Sarah E. Harris, Ozren Polasek, Mika Kähönen, Tineka Blake, Marjo-Riitta Järvelin, Rasika A. Mathias, Jing Hua Zhao, Julien Vaucher, Girish N. Nadkarni, Christopher E. Brightling
Přispěvatelé: Groningen Research Institute for Asthma and COPD (GRIAC), Wareham, Nicholas [0000-0003-1422-2993], Zhao, Jing Hua [0000-0003-4930-3582], Marten, Jonathan [0000-0001-6916-2014], Apollo - University of Cambridge Repository
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Oncology
Genome-wide association study
heart disease
VARIANTS
SUSCEPTIBILITY
Epigenesis
Genetic
AIR-FLOW OBSTRUCTION
Pulmonary Disease
Chronic Obstructive
Risk Factors
HISTORY
GWAS
EPIDEMIOLOGY
Lung
POPULATION
Cause of death
Genetics & Heredity
Aged
80 and over
education.field_of_study
COPD
Framingham Risk Score
Chronic obstructive pulmonary disease
Heart
11 Medical And Health Sciences
Middle Aged
3. Good health
Female
HEALTH
Life Sciences & Biomedicine
Adult
medicine.medical_specialty
Population
genome-wide
lungs
target
Biology
Polymorphism
Single Nucleotide
Article
03 medical and health sciences
Internal medicine
Genetics
medicine
Humans
Genetic Predisposition to Disease
Allele
education
Alleles
Aged
Asthma
Science & Technology
ta1184
Odds ratio
06 Biological Sciences
ta3121
medicine.disease
Lung function
respiratory tract diseases
030104 developmental biology
Genetic Loci
FAM13A
Immunology
Lungs
Pulmonary disease
Developmental Biology
Genome-Wide Association Study
Zdroj: Nature Genetics, 49(3), 416-425. Nature Publishing Group
Nat. Genet. 49, 416-425 (2017)
Nature genetics
Wain, L V, Shrine, N, Artigas, M S, Erzurumluoglu, A M, Noyvert, B, Bossini-Castillo, L, Obeidat, ME, Henry, A P, Portelli, M A, Hall, R J, Billington, C K, Rimington, T L, Fenech, A G, John, C, Blake, T, Jackson, V E, Allen, R J, Prins, B P, Campbell, A, Porteous, D J, Jarvelin, M R, Wielscher, M, James, A L, Hui, J, Wareham, N J, Zhao, J H, Wilson, J F, Joshi, P K, Stubbe, B, Rawal, R, Schulz, H, Imboden, M, Probst-Hensch, N M, Karrasch, S, Gieger, C, Deary, I J, Harris, S E, Marten, J, Rudan, I, Enroth, S, Gyllensten, U, Kerr, S M, Polasek, O, Kähönen, M, Surakka, I, Vitart, V, Hayward, C, Lehtimäki, T, Raitakari, O T, Evans, D M, Henderson, A J, Pennell, C E, Wang, C A, Sly, P D, Wan, E S, Busch, R, Hobbs, B D, Litonjua, A A, Sparrow, D W, Gulsvik, A, Bakke, P S, Crapo, J D, Beaty, T H, Hansel, N N, Mathias, R A, Ruczinski, I, Barnes, K C, Bossé, Y, Joubert, P, Van Den Berge, M, Brandsma, C A, Paré, P D, Sin, D D, Nickle, D C, Hao, K, Gottesman, O, Dewey, F E, Bruse, S E, Carey, D J, Kirchner, H L, Jonsson, S, Thorleifsson, G, Jonsdottir, I, Gislason, T, Stefansson, K, Schurmann, C, Nadkarni, G, Bottinger, E P, Loos, R J F, Walters, R G, Chen, Z, Millwood, I Y, Vaucher, J, Kurmi, O P, Li, L, Hansell, A L, Brightling, C, Zeggini, E, Cho, M H, Silverman, E K, Sayers, I, Trynka, G, Morris, A P, Strachan, D P, Hall, I P & Tobin, M 2017, ' Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets ', Nature Genetics, vol. 49, no. 3, pp. 416-425 . https://doi.org/10.1038/ng.3787
Wain, L V, Shrine, N, Artigas, M S, Erzurumluoglu, A M, Noyvert, B, Bossini-Castillo, L, Obeidat, M, Henry, A P, Portelli, M A, Hall, R J, Billington, C K, Rimington, T L, Fenech, A G, John, C, Blake, T, Jackson, V E, Allen, R J, Prins, B P, Campbell, A, Porteous, D J, Jarvelin, M-R, Wielscher, M, James, A L, Hui, J, Wareham, N J, Zhao, J H, Wilson, J F, Joshi, P K, Stubbe, B, Rawal, R, Schulz, H, Imboden, M, Probst-Hensch, N M, Karrasch, S, Gieger, C, Deary, I J, Harris, S E, Marten, J, Rudan, I, Enroth, S, Gyllensten, U, Kerr, S M, Polasek, O, Kähönen, M, Surakka, I, Vitart, V, Hayward, C, Lehtimäki, T & Raitakari, O T & Morris, A P 2017, ' Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets ', Nature Genetics, vol. 49, no. 3, pp. 416-425 . https://doi.org/10.1038/ng.3787
Nature Genetics
ISSN: 1546-1718
1061-4036
Popis: 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 (similar to 6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 x 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.
Databáze: OpenAIRE
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