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A genome-wide analysis of the response to inhaled β2-agonists in chronic obstructive pulmonary disease

2015; Springer Nature; Volume: 16; Issue: 4 Linguagem: Inglês

10.1038/tpj.2015.65

1473-1150

Megan Hardin, Min Hyun Cho, Merry‐Lynn McDonald, Eric Yuk Fai Wan, David A. Lomas, Harvey O. Coxson, William MacNee, Jørgen Vestbo, Julie Yates, Àlvar Agustí, Peter M. Calverley, B Celli, Courtney Crim, Stephen I. Rennard, Emiel F.�M. Wouters, P Bakke, Surya P. Bhatt, Victor Kim, Joe Ramsdell, E.A. Regan, Barry J. Make, John E. Hokanson, James D. Crapo, Terri H. Beaty, C.P. Hersh, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Nan M. Laird, Christoph Lange, Michael Cho, Stephanie Santorico, John E. Hokanson, Dawn L. DeMeo, Nadia N. Hansel, Craig P. Hersh, Peter J. Castaldi, Merry‐Lynn McDonald, Emily S. Wan, Megan Hardin, Jacqueline B. Hetmanski, Margaret M. Parker, Marilyn G. Foreman, Brian D. Hobbs, Robert Busch, Adel El-Bouiez, Peter J. Castaldi, Megan Hardin, Dandi Qiao, Elizabeth A. Regan, Eitan Halper-Stromberg, Ferdouse Begum, Sungho Won, Brittney Fredericksen, Sharon M. Lutz, David A. Lynch, Harvey O. Coxson, MeiLan K. Han, Eric A. Hoffman, Stephen M. Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, John D. Newell, Elizabeth A. Regan, James C. Ross, Raúl San Jośe Estépar, Berend C. Stoel, Juerg Tschirren, Eva M. van Rikxoort, Bram van Ginneken, George Washko, Carla G. Wilson, Mustafa Al Qaisi, Teresa Gray, Alex Kluiber, Tanya Mann, Jered Sieren, Douglas R. Stinson, Joyce Schroeder, Edwin J.R. van Beek, Robert L. Jensen, D. H. Everett, Anna Faino, Matthew Strand, Carla G. Wilson, John E. Hokanson, Jennifer L. Black‐Shinn, Gregory L. Kinney, Sharon M. Lutz, Katherine Pratte, Jeffrey L. Curtis, Carlos José Álvarez Martínez, Perry G. Pernicano, Nicola A. Hanania, Philip Alapat, Venkata Bandi, Mustafa Atik, Aladin M. Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Arun C. Nachiappan, Dawn L. DeMeo, Craig P. Hersh, George Washko, Francine L. Jacobson, R. Graham Barr, Byron Thomashow, John Austin, Belinda D’Souza, Gregory D. Pearson, Anna Rozenshtein, Neil MacIntyre, H. Page McAdams, Charlene McEvoy, Joseph Tashjian, Robert A. Wise, Nadia N. Hansel, Robert H. Brown, Karen M. Horton, Nirupama Putcha, Richard Casaburi, Alessandra Adami, János Pórszász, H. Keith Fischer, Matthew J. Budoff, Dan Cannon, Harry B. Rossiter, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Marilyn G. Foreman, Gloria Westney, Eugene A. Berkowitz, Russell P. Bowler, David A. Lynch, Richard Rosiello, David Pace, Gerard J. Criner, David Ciccolella, Francis Cordova, Chandra Dass, R D'Alonzo, Parag Desai, Michael R. Jacobs, Steven G. Kelsen, Victor Kim, A.J. Mamary, Nathaniel Marchetti, Aditti Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Gloria Vega-Sanchez, Hrudaya Nath, Mark T. Dransfield, William C. Bailey, J. Michael Wells, Surya P. Bhatt, Hrudaya Nath, Joe Ramsdell, Paul J. Friedman, Xavier Soler, Andrew Yen, Alejandro Cornellas, John D. Newell, Brad Thompson, MeiLan K. Han, Ella A. Kazerooni, Fernando D. Martínez, Joanne Billings, Tadashi Allen, Frank C. Sciurba, Divay Chandra, Joel L. Weissfeld, Carl R. Fuhrman, Jessica Bon, Antonio Anzueto, Sylvia Adams, Diego Maselli-Caceres, Mario E. Ruiz, Jean Bourbeau, Mark Fitzgerald, Pilar Hernández, K. J. Killian, Robert D. Levy, F. Maltais, D. E. O'Donnell, J. KREPELKA, Jørgen Vestbo, Emiel F.�M. Wouters, David I. Quinn, P Bakke, Mitja Košnik, Àlvar Agustí, Palma de Mallorca, Y. I. Feschenko, V. Gavrisyuk, L. P. Yashina, L. P. Yashina, William MacNee, Dave Singh, Jadwiga A. Wedzicha, Antonio Anzueto, S. Kristine Braman, Richard Casaburi, B Celli, G. Giessel, Mark H. Gotfried, Gilbert S. Greenwald, NA Hanania, D.A. Mahler, Barry J. Make, Stephen I. Rennard, Carolyn L. Rochester, Paul Scanlon, Dan Schuller, Frank C. Sciurba, Amir Sharafkhaneh, Thomas Siler, Edwin K. Silverman, Adam Wanner, Robert A. Wise, Harvey O. Coxson, Courtney Crim, Lisa Edwards, David A. Lomas, William MacNee, Edwin K. Silverman, Ruth Tal‐Singer, Jørgen Vestbo, Julie Yates, Àlvar Agustí, Peter M. Calverley, B Celli, Courtney Crim, Bruce E. Miller, William MacNee, Stephen I. Rennard, Ruth Tal‐Singer, Emiel F.�M. Wouters, Julie Yates,

Respiratory and Cough-Related Research

Short-acting β2-agonist bronchodilators are the most common medications used in treating chronic obstructive pulmonary disease (COPD). Genetic variants determining bronchodilator responsiveness (BDR) in COPD have not been identified. We performed a genome-wide association study (GWAS) of BDR in 5789 current or former smokers with COPD in one African-American and four white populations. BDR was defined as the quantitative spirometric response to inhaled β2-agonists. We combined results in a meta-analysis. In the meta-analysis, single-nucleotide polymorphisms (SNPs) in the genes KCNK1 (P=2.02 × 10−7) and KCNJ2 (P=1.79 × 10−7) were the top associations with BDR. Among African Americans, SNPs in CDH13 were significantly associated with BDR (P=5.1 × 10−9). A nominal association with CDH13 was identified in a gene-based analysis in all subjects. We identified suggestive association with BDR among COPD subjects for variants near two potassium channel genes (KCNK1 and KCNJ2). SNPs in CDH13 were significantly associated with BDR in African Americans.