DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease

Jin H. Lee, Merry Lynn N McDonald, Michael H. Cho, Emily S. Wan, Peter J. Castaldi, Gary M. Hunninghake, Nathaniel Marchetti, David A. Lynch, James D. Crapo, David A. Lomas, Harvey O. Coxson, Per S. Bakke, Edwin K. Silverman, Craig P. Hersh, Stephanie Bratschie, Rochelle Lantz, Sandra Melanson, Lori Stepp, Russell P. Bowler, Jeffrey L. CurtisMeiLan K. Han, John E. Hokanson, Barry J. Make, E. Rand Sutherland, Eugene R. Bleecker, Ronald G. Crystal, James C. Hogg, Michael A. Province, Stephen I. Rennard, Duncan C. Thomas, Thomas Croxton, Weiniu Gan, Lisa Postow, John W. Walsh, Randel Plant, Delia Prieto, Daniel Cossette, Roxanne K. Kelly, Douglas Everett, Andre Williams, Ruthie Knowles, Carla Wilson, John Hokanson, Jennifer Black-Shinn, Gregory Kinney, Michael Cho, Dawn L. DeMeo, Marilyn G. Foreman, Nadia N. Hansel, Megan E. Hardin, Jacqueline Hetmanski, Nan Laird, Christoph Lange, Sharon M. Lutz, Manuel Mattheisen, Merry Lynn McDonald, Margaret M. Parker, Elizabeth A. Regan, Stephanie Santorico, Jin Zhou, Mustafa Al Qaisi, Jaleh Akhavan, Christian W. Cox, Deanna Cusick, Jennifer G. Dy, Shoshana Ginsburg, Eric A. Hoffman, Philip F. Judy, Alex Kluiber, Alexander McKenzie, John D. Newell, John J. Reilly, James Ross, Raul San Jose Estepar, Joyce D. Schroeder, Jered Sieren, Arkadiusz Sitek, Douglas Stinson, George R. Washko, Jordan Zach, Robert Jensen, Terri Beaty, E. R. Sutherland, Homayoon Farzadegan, Samantha Bragan, Stacey Cayetano, Jeffrey Curtis, Ella Kazerooni, Nicola Hanania, Philip Alapat, Venkata Bandi, Kalpalatha Guntupalli, Elizabeth Guy, Antara Mallampalli, Charles Trinh, Mustafa Atik, Hasan Al-Azzawi, Linda Fahr, L. Alexander Frigini, David Katz, Jose Freytes, Anne Marie Marciel, Dawn DeMeo, Craig Hersh, George Washko, Francine Jacobson, Hiroto Hatabu, Peter Clarke, Ritu Gill, Andetta Hunsaker, Beatrice Trotman-Dickenson, Rachna Madan, R. Graham Barr, Byron Thomashow, John Austin, Belinda D'Souza, Neil MacIntyre, Lacey Washington, H. Page McAdams, Richard Rosiello, Timothy Bresnahan, Joseph Bradley, Sharon Kuong, Steven Meller, Suzanne Roland, Charlene McEvoy, Joseph Tashjian, Robert Wise, Nadia Hansel, Robert Brown, Gregory Diette, Karen Horton, Richard Casaburi, Janos Porszasz, Hans Fischer, Matt Budoff, Mehdi Rambod, Michael E. DeBakey, Amir Sharafkhaneh, Hirani Kamal, Roham Darvishi, Marc Willis, Susan Pinero, Arun Nachiappan, Collin Bray, Carlos Farinas, Dennis Niewoehner, Quentin Anderson, Kathryn Rice, Audrey Caine, Marilyn Foreman, Gloria Westney, Eugene Berkowitz, Russell Bowler, David Lynch, Joyce Schroeder, Valerie Hale, John Armstrong, Debra Dyer, Jonathan Chung, Christian Cox, Gerard Criner, Victor Kim, Aditi Satti, A. James Mamary, Robert Steiner, Chandra Dass, Libby Cone, William Bailey, Mark Dransfield, Michael Wells, Surya Bhatt, Hrudaya Nath, Satinder Singh, Joe Ramsdell, Paul Friedman, Alejandro Cornellas, John Newell, Edwin van Beek, Fernando Martinez, MeiLan Han, Christine Wendt, Tadashi Allen, Frank Sciurba, Joel Weissfeld, Carl Fuhrman, Jessica Bon, Danielle Hooper, Antonio Anzueto, Sandra Adams, Carlos Orozco, Mario Ruiz, Amy Mumbower, Ariel Kruger, Carlos Restrepo, Michael Lane, Y. Ivanov, K. Kostov, J. Bourbeau, M. Fitzgerald, P. Hernandez, K. Killian, R. Levy, F. Maltais, D. O'Donnell, J. Krepelka, J. Vestbo, E. Wouters, D. Quinn, P. Bakke, M. Kosnik, A. Agusti, J. Sauleda, P. de Mallorca, Y. Feschenko, V. Gavrisyuk, L. Yashina, N. Monogarova, P. Calverley, D. Lomas, W. MacNee, D. Singh, J. Wedzicha, A. Anzueto, A. Braman, R. Casaburi, B. Celli, G. Giessel, M. Gotfried, G. Greenwald, N. Hanania, D. Mahler, B. Make, S. Rennard, C. Rochester, P. Scanlon, D. Schuller, F. Sciurba, A. Sharafkhaneh, T. Siler, E. Silverman, A. Wanner, R. Wise, R. ZuWallack, H. Coxson, C. Crim, L. Edwards, D. Lomas, W. MacNee, P. Calverley, W. MacNee, E. Silverman, B. Celli, S. Rennard, R. Tal Singer, J. Yates, C. Crim, B. Miller, R. Tal-Singer, J. Yates, J. Vestbo, A. Agusti, E. Wouters

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.Methods: We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) <0.7 and FEV1 < 80% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLCCT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLCCT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis.Results: Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, β = 0.42L, P = 4.66 × 10-8).Conclusions: In COPD, TLCCT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD.

Original languageEnglish (US)
Article number97
JournalRespiratory research
Volume15
Issue number1
DOIs
StatePublished - Aug 20 2014

Bibliographical note

Publisher Copyright:
© 2014 Lee et al.; licensee BioMed Central Ltd.

Keywords

  • Chronic obstructive
  • DNAH5
  • Genome-wide association analysis
  • Hyperinflation
  • Pulmonary disease
  • Total lung capacity

Fingerprint

Dive into the research topics of 'DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease'. Together they form a unique fingerprint.

Cite this