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. Curtis; MeiLan 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

doi:10.1186/s12931-014-0097-y

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 journal › Article › peer-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 (TLC_CT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLC_CT, 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, TLC_CT 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 language	English (US)
Article number	97
Journal	Respiratory research
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s12931-014-0097-y
State	Published - 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

Publisher link

10.1186/s12931-014-0097-y

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Lee, J. H., McDonald, M. L. N., Cho, M. H., Wan, E. S., Castaldi, P. J., Hunninghake, G. M., Marchetti, N., Lynch, D. A., Crapo, J. D., Lomas, D. A., Coxson, H. O., Bakke, P. S., Silverman, E. K., Hersh, C. P., Bratschie, S., Lantz, R., Melanson, S., Stepp, L., Bowler, R. P., ... Wouters, E. (2014). DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease. Respiratory research, 15(1), Article 97. https://doi.org/10.1186/s12931-014-0097-y

Lee, JH, McDonald, MLN, Cho, MH, Wan, ES, Castaldi, PJ, Hunninghake, GM, Marchetti, N, Lynch, DA, Crapo, JD, Lomas, DA, Coxson, HO, Bakke, PS, Silverman, EK, Hersh, CP, Bratschie, S, Lantz, R, Melanson, S, Stepp, L, Bowler, RP, Curtis, JL, Han, MK, Hokanson, JE, Make, BJ, Sutherland, ER, Bleecker, ER, Crystal, RG, Hogg, JC, Province, MA, Rennard, SI, Thomas, DC, Croxton, T, Gan, W, Postow, L, Walsh, JW, Plant, R, Prieto, D, Cossette, D, Kelly, RK, Everett, D, Williams, A, Knowles, R, Wilson, C, Hokanson, J, Black-Shinn, J, Kinney, G, Cho, M, DeMeo, DL, Foreman, MG, Hansel, NN, Hardin, ME, Hetmanski, J, Laird, N, Lange, C, Lutz, SM, Mattheisen, M, McDonald, ML, Parker, MM, Regan, EA, Santorico, S, Zhou, J, Qaisi, MA, Akhavan, J, Cox, CW, Cusick, D, Dy, JG, Ginsburg, S, Hoffman, EA, Judy, PF, Kluiber, A, McKenzie, A, Newell, JD, Reilly, JJ, Ross, J, Estepar, RSJ, Schroeder, JD, Sieren, J, Sitek, A, Stinson, D, Washko, GR, Zach, J, Jensen, R, Beaty, T, Sutherland, ER, Farzadegan, H, Bragan, S, Cayetano, S, Curtis, J, Kazerooni, E, Hanania, N, Alapat, P, Bandi, V, Guntupalli, K, Guy, E, Mallampalli, A, Trinh, C, Atik, M, Al-Azzawi, H, Fahr, L, Frigini, LA, Katz, D, Freytes, J, Marciel, AM, DeMeo, D, Hersh, C, Washko, G, Jacobson, F, Hatabu, H, Clarke, P, Gill, R, Hunsaker, A, Trotman-Dickenson, B, Madan, R, Barr, RG, Thomashow, B, Austin, J, D'Souza, B, MacIntyre, N, Washington, L, McAdams, HP, Rosiello, R, Bresnahan, T, Bradley, J, Kuong, S, Meller, S, Roland, S, McEvoy, C, Tashjian, J, Wise, R, Hansel, N, Brown, R, Diette, G, Horton, K, Casaburi, R, Porszasz, J, Fischer, H, Budoff, M, Rambod, M, DeBakey, ME, Sharafkhaneh, A, Kamal, H, Darvishi, R, Willis, M, Pinero, S, Nachiappan, A, Bray, C, Farinas, C, Niewoehner, D, Anderson, Q, Rice, K, Caine, A, Foreman, M, Westney, G, Berkowitz, E, Bowler, R, Lynch, D, Schroeder, J, Hale, V, Armstrong, J, Dyer, D, Chung, J, Cox, C, Criner, G, Kim, V, Satti, A, Mamary, AJ, Steiner, R, Dass, C, Cone, L, Bailey, W, Dransfield, M, Wells, M, Bhatt, S, Nath, H, Singh, S, Ramsdell, J, Friedman, P, Cornellas, A, Newell, J, van Beek, E, Martinez, F, Han, M, Wendt, C , Allen, T, Sciurba, F, Weissfeld, J, Fuhrman, C, Bon, J, Hooper, D, Anzueto, A, Adams, S, Orozco, C, Ruiz, M, Mumbower, A, Kruger, A, Restrepo, C, Lane, M, Ivanov, Y, Kostov, K, Bourbeau, J, Fitzgerald, M, Hernandez, P, Killian, K, Levy, R, Maltais, F, O'Donnell, D, Krepelka, J, Vestbo, J, Wouters, E, Quinn, D, Bakke, P, Kosnik, M, Agusti, A, Sauleda, J, de Mallorca, P, Feschenko, Y, Gavrisyuk, V, Yashina, L, Monogarova, N, Calverley, P, Lomas, D, MacNee, W, Singh, D, Wedzicha, J, Anzueto, A, Braman, A, Casaburi, R, Celli, B, Giessel, G, Gotfried, M, Greenwald, G, Hanania, N, Mahler, D, Make, B, Rennard, S, Rochester, C, Scanlon, P, Schuller, D, Sciurba, F, Sharafkhaneh, A, Siler, T, Silverman, E, Wanner, A, Wise, R, ZuWallack, R, Coxson, H, Crim, C, Edwards, L, Lomas, D, MacNee, W, Calverley, P, MacNee, W, Silverman, E, Celli, B, Rennard, S, Singer, RT, Yates, J, Crim, C, Miller, B, Tal-Singer, R, Yates, J, Vestbo, J, Agusti, A & Wouters, E 2014, 'DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease', Respiratory research, vol. 15, no. 1, 97. https://doi.org/10.1186/s12931-014-0097-y

@article{8994e6c1a111483c8478006c24f89c6f,

title = "DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease",

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.",

keywords = "Chronic obstructive, DNAH5, Genome-wide association analysis, Hyperinflation, Pulmonary disease, Total lung capacity",

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

note = "Publisher Copyright: {\textcopyright} 2014 Lee et al.; licensee BioMed Central Ltd.",

year = "2014",

month = aug,

day = "20",

doi = "10.1186/s12931-014-0097-y",

language = "English (US)",

volume = "15",

journal = "Respiratory research",

issn = "1465-9921",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease

AU - Lee, Jin H.

AU - McDonald, Merry Lynn N

AU - Cho, Michael H.

AU - Wan, Emily S.

AU - Castaldi, Peter J.

AU - Hunninghake, Gary M.

AU - Marchetti, Nathaniel

AU - Lynch, David A.

AU - Crapo, James D.

AU - Lomas, David A.

AU - Coxson, Harvey O.

AU - Bakke, Per S.

AU - Silverman, Edwin K.

AU - Hersh, Craig P.

AU - Bratschie, Stephanie

AU - Lantz, Rochelle

AU - Melanson, Sandra

AU - Stepp, Lori

AU - Bowler, Russell P.

AU - Curtis, Jeffrey L.

AU - Han, MeiLan K.

AU - Hokanson, John E.

AU - Make, Barry J.

AU - Sutherland, E. Rand

AU - Bleecker, Eugene R.

AU - Crystal, Ronald G.

AU - Hogg, James C.

AU - Province, Michael A.

AU - Rennard, Stephen I.

AU - Thomas, Duncan C.

AU - Croxton, Thomas

AU - Gan, Weiniu

AU - Postow, Lisa

AU - Walsh, John W.

AU - Plant, Randel

AU - Prieto, Delia

AU - Cossette, Daniel

AU - Kelly, Roxanne K.

AU - Everett, Douglas

AU - Williams, Andre

AU - Knowles, Ruthie

AU - Wilson, Carla

AU - Hokanson, John

AU - Black-Shinn, Jennifer

AU - Kinney, Gregory

AU - Cho, Michael

AU - DeMeo, Dawn L.

AU - Foreman, Marilyn G.

AU - Hansel, Nadia N.

AU - Hardin, Megan E.

AU - Hetmanski, Jacqueline

AU - Laird, Nan

AU - Lange, Christoph

AU - Lutz, Sharon M.

AU - Mattheisen, Manuel

AU - McDonald, Merry Lynn

AU - Parker, Margaret M.

AU - Regan, Elizabeth A.

AU - Santorico, Stephanie

AU - Zhou, Jin

AU - Qaisi, Mustafa Al

AU - Akhavan, Jaleh

AU - Cox, Christian W.

AU - Cusick, Deanna

AU - Dy, Jennifer G.

AU - Ginsburg, Shoshana

AU - Hoffman, Eric A.

AU - Judy, Philip F.

AU - Kluiber, Alex

AU - McKenzie, Alexander

AU - Newell, John D.

AU - Reilly, John J.

AU - Ross, James

AU - Estepar, Raul San Jose

AU - Schroeder, Joyce D.

AU - Sieren, Jered

AU - Sitek, Arkadiusz

AU - Stinson, Douglas

AU - Washko, George R.

AU - Zach, Jordan

AU - Jensen, Robert

AU - Beaty, Terri

AU - Sutherland, E. R.

AU - Farzadegan, Homayoon

AU - Bragan, Samantha

AU - Cayetano, Stacey

AU - Curtis, Jeffrey

AU - Kazerooni, Ella

AU - Hanania, Nicola

AU - Alapat, Philip

AU - Bandi, Venkata

AU - Guntupalli, Kalpalatha

AU - Guy, Elizabeth

AU - Mallampalli, Antara

AU - Trinh, Charles

AU - Atik, Mustafa

AU - Al-Azzawi, Hasan

AU - Fahr, Linda

AU - Frigini, L. Alexander

AU - Katz, David

AU - Freytes, Jose

AU - Marciel, Anne Marie

AU - DeMeo, Dawn

AU - Hersh, Craig

AU - Washko, George

AU - Jacobson, Francine

AU - Hatabu, Hiroto

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AU - Schuller, D.

AU - Sciurba, F.

AU - Sharafkhaneh, A.

AU - Siler, T.

AU - Silverman, E.

AU - Wanner, A.

AU - Wise, R.

AU - ZuWallack, R.

AU - Coxson, H.

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AU - Vestbo, J.

AU - Agusti, A.

AU - Wouters, E.

PY - 2014/8/20

Y1 - 2014/8/20

N2 - 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.

AB - 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.

KW - Chronic obstructive

KW - DNAH5

KW - Genome-wide association analysis

KW - Hyperinflation

KW - Pulmonary disease

KW - Total lung capacity

UR - http://www.scopus.com/inward/record.url?scp=84908157737&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908157737&partnerID=8YFLogxK

U2 - 10.1186/s12931-014-0097-y

DO - 10.1186/s12931-014-0097-y

M3 - Article

C2 - 25134640

AN - SCOPUS:84908157737

SN - 1465-9921

VL - 15

JO - Respiratory research

JF - Respiratory research

IS - 1

M1 - 97

ER -

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

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