Common genetic variants associated with resting oxygenation in chronic obstructive pulmonary disease
Merry-Lynn N McDonald, Michael H Cho, Inga-Cecilie Sørheim, Sharon M Lutz, Peter J Castaldi, David A Lomas, Harvey O Coxson, Lisa D Edwards, William MacNee, Jørgen Vestbo, Julie C Yates, Alvar Agusti, Peter M A Calverley, Bartolome Celli, Courtney Crim, Stephen I Rennard, Emiel F M Wouters, Per Bakke, Ruth Tal-Singer, Bruce E Miller, Amund Gulsvik, Richard Casaburi, J Michael Wells, Elizabeth A Regan, Barry J Make, John E Hokanson, Christoph Lange, James D Crapo, Terri H Beaty, Edwin K Silverman, Craig P Hersh, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints and COPDGene Investigators, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Rochelle Lantz, Lori Stepp, Sandra Melanson, Terri Beaty, Nan Laird, Christoph Lange, Michael Cho, Stephanie Santorico, John Hokanson, Dawn DeMeo, Nadia Hansel, Craig Hersh, Peter Castaldi, Merry-Lynn McDonald, Jin Zhou, Manuel Mattheisen, Emily Wan, Megan Hardin, Jacqueline Hetmanski, Margaret Parker, Tanda Murray, Marilyn Foreman, Sharon M Lutz, Elizabeth Regan, Edwin K Silverman, David Lynch, Joyce Schroeder, John Newell Jr, John Reilly, Harvey Coxson, Philip Judy, Eric Hoffman, George Washko, Raul San Jose Estepar, James Ross, Mustafa Al Qaisi, Jordan Zach, Alex Kluiber, Jered Sieren, Tanya Mann, Deanna Richert, Alexander McKenzie, Jaleh Akhavan, Douglas Stinson, Christian W Cox, Deanna Cusick, Jennifer G Dy, Shoshana Ginsburg, Arkadiusz Sitek, Edwin van Beek, Robert Jensen, Homayoon Farzadegan, Stacey Meyerer, Shivam Chandan, Samantha Bragan, Douglas Everett, Andre Williams, Carla Wilson, Anna Forssen, Amber Powell, Joe Piccoli, John Hokanson, Marci Sontag, Jennifer Black-Shinn, Gregory Kinney, Sharon Lutz, Jeffrey Curtis, Ella Kazerooni, Nicola Hanania, Philip Alapat, Venkata Bandi, Kalpalatha Guntupalli, Elizabeth Guy, Antara Mallampalli, Charles Trinh, Mustafa Atik, Hasan Al-Azzawi, Marc Willis, Susan Pinero, Linda Fahr, Arun Nachiappan, Collin Bray, Alexander Frigini, Carlos Farinas, 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 Jr, 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, Amir Sharafkhaneh, Charles Trinh, Hirani Kamal, Roham Darvishi, Marc Willis, Susan Pinero, Linda Fahr, Arun Nachiappan, Collin Bray, Alexander Frigini, Carlos Farinas, David Katz, Jose Freytes, Anne Marie Marciel, Dennis Niewoehner, Quentin Anderson, Kathryn Rice, Audrey Caine, Marilyn Foreman, Gloria Westney, Eugene Berkowitz, Russell Bowler, David Lynch, Joyce Schroeder, Valerie Hale, John Armstrong 2nd, Debra Dyer, Jonathan Chung, Christian Cox, Gerard Criner, Victor Kim, Nathaniel Marchetti, 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 Jr, Edwin J R van Beck, Fernando Martinez, Mei Lan Han, Ella Kazerooni, 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, Y Feschenko, V Gavrisyuk, L Yashina, N Monogarova, P Calverley, D Lomas, W MacNee, D Singh, J Wedzicha, A Anzueto, S 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, E Silverman, R Tal Singer, J Vestbo, J Yates, A Agusti, P Calverley, B Celli, C Crim, B Miller, W MacNee, S Rennard, R Tal-Singer, E Wouters, J Yates, Merry-Lynn N McDonald, Michael H Cho, Inga-Cecilie Sørheim, Sharon M Lutz, Peter J Castaldi, David A Lomas, Harvey O Coxson, Lisa D Edwards, William MacNee, Jørgen Vestbo, Julie C Yates, Alvar Agusti, Peter M A Calverley, Bartolome Celli, Courtney Crim, Stephen I Rennard, Emiel F M Wouters, Per Bakke, Ruth Tal-Singer, Bruce E Miller, Amund Gulsvik, Richard Casaburi, J Michael Wells, Elizabeth A Regan, Barry J Make, John E Hokanson, Christoph Lange, James D Crapo, Terri H Beaty, Edwin K Silverman, Craig P Hersh, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints and COPDGene Investigators, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Rochelle Lantz, Lori Stepp, Sandra Melanson, Terri Beaty, Nan Laird, Christoph Lange, Michael Cho, Stephanie Santorico, John Hokanson, Dawn DeMeo, Nadia Hansel, Craig Hersh, Peter Castaldi, Merry-Lynn McDonald, Jin Zhou, Manuel Mattheisen, Emily Wan, Megan Hardin, Jacqueline Hetmanski, Margaret Parker, Tanda Murray, Marilyn Foreman, Sharon M Lutz, Elizabeth Regan, Edwin K Silverman, David Lynch, Joyce Schroeder, John Newell Jr, John Reilly, Harvey Coxson, Philip Judy, Eric Hoffman, George Washko, Raul San Jose Estepar, James Ross, Mustafa Al Qaisi, Jordan Zach, Alex Kluiber, Jered Sieren, Tanya Mann, Deanna Richert, Alexander McKenzie, Jaleh Akhavan, Douglas Stinson, Christian W Cox, Deanna Cusick, Jennifer G Dy, Shoshana Ginsburg, Arkadiusz Sitek, Edwin van Beek, Robert Jensen, Homayoon Farzadegan, Stacey Meyerer, Shivam Chandan, Samantha Bragan, Douglas Everett, Andre Williams, Carla Wilson, Anna Forssen, Amber Powell, Joe Piccoli, John Hokanson, Marci Sontag, Jennifer Black-Shinn, Gregory Kinney, Sharon Lutz, Jeffrey Curtis, Ella Kazerooni, Nicola Hanania, Philip Alapat, Venkata Bandi, Kalpalatha Guntupalli, Elizabeth Guy, Antara Mallampalli, Charles Trinh, Mustafa Atik, Hasan Al-Azzawi, Marc Willis, Susan Pinero, Linda Fahr, Arun Nachiappan, Collin Bray, Alexander Frigini, Carlos Farinas, 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 Jr, 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, Amir Sharafkhaneh, Charles Trinh, Hirani Kamal, Roham Darvishi, Marc Willis, Susan Pinero, Linda Fahr, Arun Nachiappan, Collin Bray, Alexander Frigini, Carlos Farinas, David Katz, Jose Freytes, Anne Marie Marciel, Dennis Niewoehner, Quentin Anderson, Kathryn Rice, Audrey Caine, Marilyn Foreman, Gloria Westney, Eugene Berkowitz, Russell Bowler, David Lynch, Joyce Schroeder, Valerie Hale, John Armstrong 2nd, Debra Dyer, Jonathan Chung, Christian Cox, Gerard Criner, Victor Kim, Nathaniel Marchetti, 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 Jr, Edwin J R van Beck, Fernando Martinez, Mei Lan Han, Ella Kazerooni, 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, Y Feschenko, V Gavrisyuk, L Yashina, N Monogarova, P Calverley, D Lomas, W MacNee, D Singh, J Wedzicha, A Anzueto, S 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, E Silverman, R Tal Singer, J Vestbo, J Yates, A Agusti, P Calverley, B Celli, C Crim, B Miller, W MacNee, S Rennard, R Tal-Singer, E Wouters, J Yates
Abstract
Hypoxemia is a major complication of chronic obstructive pulmonary disease (COPD) that correlates with disease prognosis. Identifying genetic variants associated with oxygenation may provide clues for deciphering the heterogeneity in prognosis among patients with COPD. However, previous genetic studies have been restricted to investigating COPD candidate genes for association with hypoxemia. To report results from the first genome-wide association study (GWAS) of resting oxygen saturation (as measured by pulse oximetry [Spo2]) in subjects with COPD, we performed a GWAS of Spo2 in two large, well characterized COPD populations: COPDGene, including both the non-Hispanic white (NHW) and African American (AA) groups, and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We identified several suggestive loci (P < 1 × 10(-5)) associated with Spo2 in COPDGene in the NHW (n = 2810) and ECLIPSE (n = 1758) groups, and two loci on chromosomes 14 and 15 in the AA group (n = 820) from COPDGene achieving a level of genome-wide significance (P < 5 × 10(-8)). The chromosome 14 single-nucleotide polymorphism, rs6576132, located in an intergenic region, was nominally replicated (P < 0.05) in the NHW group from COPDGene. The chromosome 15 single-nucleotide polymorphisms were rare in subjects of European ancestry, so the results could not be replicated. The chromosome 15 region contains several genes, including TICRR and KIF7, and is proximal to RHCG (Rh family C glyocoprotein gene). We have identified two loci associated with resting oxygen saturation in AA subjects with COPD, and several suggestive regions in subjects of European descent with COPD. Our study highlights the importance of investigating the genetics of complex traits in different racial groups.
Trial registration: ClinicalTrials.gov NCT00608764.
Keywords: chronic obstructive pulmonary disease; genome-wide association study; hypoxemia; oxygen saturation; pulse oximetry.
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Source: PubMed