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6. Lung Segmentation of MR Images: A Review

Author

Ivanovska, Tatyana, Hegenscheid, Katrin, Laqua, René, Gläser, Sven, Ewert, Ralf, Völzke, Henry, Hege, Hans-Christian, Series editor, Hoffman, David, Series editor, Johnson, Christopher R., Series editor, Polthier, Konrad, Series editor, Rumpf, Martin, Series editor, Linsen, Lars, editor, and Hamann, Bernd, editor

Published
2016
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19. FOCUS 2: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia

Author

Low, Donald E., File, Thomas M., Jr, Eckburg, Paul B., Talbot, George H., David Friedland, H., Lee, Jon, Llorens, Lily, Critchley, Ian A., Thye, Dirk A., Corral, Jorge, Giugno, Eduardo, Gonzalez Arzac, Maria del Rosario, Maurizi, Diego, Altclas, Javier, Ambasch, Germán, Jasovich, Abel, Minguez, Angel Ramon, Oliva, Maria Eugenia, Teglia, Osvaldo, Bergallo, Carlos, Mastruzzo, Maria Antonia, Isabel Morera, Graciana, Scapellato, Pabio Gustavo, Lamberghini, Ricardo, Mykietiuk, Analia, Remolif, Christian, Barros Monge, Manuel Jose, Enriqueta Campos Barker, Maria Isabel, Chernilo Steinmann, Sara Mireya, Gaete Gutierrez, Pablo Antonio, Muñoz Vejar, Sylvia Susana, Calvo Arellano, Mario Andres, Chahin Anania, Carolina Eugenia, Jauregui Cruz, Arturo, Amaya Tapia, Gerardo, Acuna Kaldman, Moises, Noriega, Eduardo, Matos Prado, Eduardo Demetrio, Ramos, Carlos, Andreeva, Irina, Abyshev, Rashad, Antonovsky, Yuri A., Balyuzek, Marina, Esina, Alla L., Gorelov, Alexander, Khrustalev, Oleg A., Kozlov, Roman S., Novozhenok, Vladislav, Popova, Veronika B., Sobchenko, Svetlana, Trofimov, Vasily, Yakovlev, Sergey, Zhidkov, Konstantin, Ambert, Luminta Gabriela, Fierbinteau, Carmen Georgeta, Ionescu, Valentina, Muresan, Mihai Marius, Tanaseanu, Cristina Mihaela, Georgiev, Ognian, Hodzhev, Valdimir, Marinov, Rosen, Metev, Hristo, Peneva, Marinka, Popov, Dimitar, Simeonova, Milkana, Krastins, Ivars, Lovcinovsk, Viktors, Silins, Viesturs, Svarcberga, Vita, Bargon, Joachim, Bauer, Thorsten, Bergmann, Rolf, Meyer, F.J., Mueller, Thomas, Welte, Tobias, Glaeser, Sven, Hammerl, Peter, Kern, Hartmut, Krueger, Stefan, Kujath, Peter, Lies, Achim, Schaberg, Tom, Schmalz, Oliver, Schütte, Wolfgang, Chazan, Ryszarda, Górecka, Dorota, Rogala, Barbara, Antczak, Adam, Grodzicki, Tomasz, JahnzRö, Karina, Milanowski, Janusz, Nalepa, Piotr, Wróbel-Rajzer, Malgorzata, Szelerska-Twardosz, Hanna, GrzelewskaRzymowska, Iwona, Kachel, Tomasz, Marciniak, Andrzej, Panaszek, Bernard, Szczeklik, Andrzej, Kozielski, Jerzy, Harat, Rafal, Jastrzebsk, Dariusz, Juszczak, Jacek, Labij, Violetta, Vetter, Norbert, Bolitschek, Josef, Eckmayr, Josef, Molnár, Sándor, Pápai-Székely, Zsolt, Szegedi, Janos, Vinkler, Ilona, Borscchivskyy, Mykhaylo, Dziublyk, Oleksandr, Dzyak, Georgiy V., Kraydaschenko, Oleg, Mostovoy, Yuriy M., Rudyk, Iurii S., Sushko, Viktor, Vizir, Vadim, Bhattacharya, Amal Kumar, Chakrapan, Mahabala, DʼSouza, George, Malpani, G.S., Mehta, Parthiv, Rao, K.N. Mohar, and Talwar, Deepak

Published
2011
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20. Autoren und Autorinnen

Author

Allelein, Stephanie, Aringer, Martin, Bals, Robert, Barthel, Andreas, Benzing, Thomas, Beuers, Ulrich, Bischoff, Stephan C., Bonella, Francesco, Bornstein, Stefan R., Böttger, Priyanka, Böttler, Tobias, Brinkkötter, Paul, Bubel, Sebastian, Buerke, Michael, Daniel, Jan-Marcus, Eckardt, Lars, Eisenmann, Stephan, Ellenrieder, Volker, Ewert, Ralf, Gallmeier, Eike, Gläser, Sven, Gliem, Nina, Gress, Thomas M., Gruber, Matthias, Heiss, Christian, Hohenester, Simon, Hoyer, Daniel, Hoyer, Joachim, Iglseder, Bernhard, Keyßer, Gernot, Koch, Christian A., Lange, Danica, Lordick, Florian, Ludwig, Christiane, Lütjohann, Dieter, Malfertheiner, Peter, Möller, Miriam, Moritz, Stefan, Müller-Tidow, Carsten, Neuendorff, Nina Rosa, Neumann-Haefelin, Christoph, Omlor, Albert, Roller, Susanne, Rump, Lars Christian, Sachs, Ulrich J., Sasse, André, Schäfer, Christoph, Schmidt, Bernd, Schott, Artjom, Schott, Matthias, Schultheiß, Michael, Schulz, Christian, Schütte, Wolfgang, Sedding, Daniel, Singler, Katrin, Spranger, Joachim, Stallmach, Andreas, Thimme, Robert, Thol, Jens, Tongers, Jörn, Tsourdi, Elena, Vogt, Alexander, Walldorf, Jens, Wasmer, Kristina, Weingärtner, Oliver, and Welsner, Matthias

Published
2023
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21. Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis: long-term results of the INSIGHTS-IPF registry

Author

Behr, Juergen, Prasse, Antje, Wirtz, Hubert, Koschel, Dirk, Pittrow, David, Held, Matthias, Klotsche, Jens, Andreas, Stefan, Claussen, Martin, Grohe, Christian, Wilkens, Henrike, Hagmeyer, Lars, Skowasch, Dirk, Meyer, Joachim F., Kirschner, Joachim, Glaeser, Sven, Kahn, Nicolas, Welte, Tobias, Neurohr, Claus, Schwaiblmair, Martin, Bahmer, Thomas, Oqueka, Tim, Frankenberger, Marion, Kreuter, Michael, Behr, Juergen, Prasse, Antje, Wirtz, Hubert, Koschel, Dirk, Pittrow, David, Held, Matthias, Klotsche, Jens, Andreas, Stefan, Claussen, Martin, Grohe, Christian, Wilkens, Henrike, Hagmeyer, Lars, Skowasch, Dirk, Meyer, Joachim F., Kirschner, Joachim, Glaeser, Sven, Kahn, Nicolas, Welte, Tobias, Neurohr, Claus, Schwaiblmair, Martin, Bahmer, Thomas, Oqueka, Tim, Frankenberger, Marion, and Kreuter, Michael

Abstract

Objective: There is a paucity of observational data on antifibrotic therapy for idiopathic pulmonary fibrosis (IPF). We aimed to assess the course of disease of IPF patients with and without antifibrotic therapy under real-life conditions. Methods: We analysed data from a non-interventional, prospective cohort study of consecutively enrolled IPF patients from 20 interstitial lung disease expert centres in Germany. Data quality was ensured by automated plausibility checks, on-site monitoring, and source data verification. Propensity scores were applied to account for known differences in baseline characteristics between patients with and without antifibrotic therapy. Results: Among the 588 patients suitable for analysis, the mean +/- so age was 69.8 +/- 9.1 years, and 81.0% were male. The mean +/- so duration of disease since diagnosis was 1.8 +/- 3.4 years. The mean +/- SD value at baseline for forced vital capacity (FVC) and diffusion capacity (D-LCO) were 68.6 +/- 18.8% predicted and 37.8 +/- 18.5% predicted, respectively. During a mean +/- so follow-up of 1.2 +/- 0.7 years, 194 (33.0%) patients died. The 1-year and 2-year survival rates were 87% versus 46% and 62% versus 21%, respectively, for patients with versus without antifibrotic therapy. The risk of death was 37% lower in patients with antifibrotic therapy (hazard ratio 0.63, 95% CI 0.45; 0.87; p=0.005). The results were robust (and remained statistically significant) on multivariable analysis. Overall decline of FVC and D-LCO was slow and did not differ significantly between patients with or without antifibrotic therapy. Conclusions: Survival was significantly higher in IPF patients with antifibrotic therapy, but the course of lung function parameters was similar in patients with and without antifibrotic therapy. This su vests that in clinical practice, premature mortality of IPF patients eventually occurs despite stable measurements for FVC and D-LCO.

Published
2020

24. Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Author

Graff, Mariaelisa, Scott, Robert A., Justice, Anne E., Young, Kristin L., Feitosa, Mary F., Barata, Llilda, Winkler, Thomas W., Chu, Audrey Y., Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L., den Hoed, Marcel, Ahluwalia, Tarunveer S., Qi, Qibin, Ngwa, Julius S., Renström, Frida, Quaye, Lydia, Eicher, John D., Hayes, James E., Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E., Zhang, Weihua, Zhao, Wei, Griffin, Paula J., Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M., Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E., Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V., Whitfield, John B., Zhao, Jing Hua, Stringham, Heather M., Lyytikainen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J., Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F., Cadby, Gemma, Tanaka, Toshiko, Magl, Reedlk, Van der Most, Peter J., Jackson, Anne U., Bragg-Gresham, Jennifer L., Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Asa, Snitker, Soren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S., Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N., Bergmann, Sven, Bertoni, Alain G., Blangero, John, Bonnefond, Amelle, Bonnycastle, Lori L., Borja, Judith B., Brage, Soren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S., Collins, Francis S., Corre, Tanguy, Smith, George Davey, Delgado, Graciela E., Dueker, Nicole, Doerr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Faul, Jessica D., Fu, Mao, Faerch, Kristine, Gieger, Christian, Glaeser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D., Havulinna, Aki S., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Holmens, Oddgeir L., Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kahonen, Nina, James, Alan L., Jansson, John-Olov, Jhun, Min A., Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A., Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaloy, Kirsti, Kahonen, Mika, Lakka, Timo A., Launer, Lenore J., Lehne, Benjamin, Lindgren, Cecilia M., Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L., Montgomery, Grant W., De Moor, Marleen H. M., Mulas, Antonella, Mueller-Nurasyid, Martina, Musk, A. W., Mannikko, Reija, Mannisto, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A., Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A., Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rawal, Rajesh, Ridker, Paul M., Rose, Lynda M., Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A., Savonen, Kai, Scott, William R., Sanna, Serena, Shuldiner, Alan R., Sidney, Steve, Silbernagel, Guenther, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Stancakova, Alena, Sternfeld, Barbara, Swift, Amy J., Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothee, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V., Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Zubair, Niha, Haiman, Christopher A., Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Perusse, Louis, Wilson, James F., Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A., Toenjes, Anke, Bandinelli, Stefania, Palmer, Lyle J., Kardia, Sharon L. R., Rauramaa, Rainer, Sorensen, Thorkild I. A., Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W. J. H., de Geus, Eco J. C., Boomsma, Dorret I., Lehtimaki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G., Kuh, Diana, Liu, Yongmei, Linneberg, Allan, Maerz, Winfried, Strauch, Konstantin, Kivimaki, Mika, Harris, Tamara B., Gudnason, Vilmundur, Voelzke, Henry, Qi, Lu, Jarvelin, Marjo-Riitta, Chambers, John C., Kooner, Jaspal S., Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J., Langenberg, Claudia, Weir, David R., Porteous, David J., Boerwinkle, Eric, Chasman, Daniel I., Abecasis, Goncalo R., Barroso, Ines, McCarthy, Mark I., Frayling, Timothy M., O'Connell, Jeffrey R., van Duijn, Cornelia M., Boehnke, Michael, Heid, Iris M., Mohlke, Karen L., Strachan, David P., Fox, Caroline S., Liu, Ching-Ti, Hirschhorn, Joel N., Klein, Robert J., Johnson, Andrew D., Borecki, Ingrid B., Franks, Paul W., North, Kari E., Cupples, L. Adrienne, Loos, Ruth J. F., Kilpelainen, Tuomas O., Graff, Mariaelisa, Scott, Robert A., Justice, Anne E., Young, Kristin L., Feitosa, Mary F., Barata, Llilda, Winkler, Thomas W., Chu, Audrey Y., Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L., den Hoed, Marcel, Ahluwalia, Tarunveer S., Qi, Qibin, Ngwa, Julius S., Renström, Frida, Quaye, Lydia, Eicher, John D., Hayes, James E., Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E., Zhang, Weihua, Zhao, Wei, Griffin, Paula J., Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M., Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E., Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V., Whitfield, John B., Zhao, Jing Hua, Stringham, Heather M., Lyytikainen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J., Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F., Cadby, Gemma, Tanaka, Toshiko, Magl, Reedlk, Van der Most, Peter J., Jackson, Anne U., Bragg-Gresham, Jennifer L., Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Asa, Snitker, Soren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S., Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N., Bergmann, Sven, Bertoni, Alain G., Blangero, John, Bonnefond, Amelle, Bonnycastle, Lori L., Borja, Judith B., Brage, Soren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S., Collins, Francis S., Corre, Tanguy, Smith, George Davey, Delgado, Graciela E., Dueker, Nicole, Doerr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Faul, Jessica D., Fu, Mao, Faerch, Kristine, Gieger, Christian, Glaeser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D., Havulinna, Aki S., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Holmens, Oddgeir L., Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kahonen, Nina, James, Alan L., Jansson, John-Olov, Jhun, Min A., Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A., Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaloy, Kirsti, Kahonen, Mika, Lakka, Timo A., Launer, Lenore J., Lehne, Benjamin, Lindgren, Cecilia M., Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L., Montgomery, Grant W., De Moor, Marleen H. M., Mulas, Antonella, Mueller-Nurasyid, Martina, Musk, A. W., Mannikko, Reija, Mannisto, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A., Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A., Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rawal, Rajesh, Ridker, Paul M., Rose, Lynda M., Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A., Savonen, Kai, Scott, William R., Sanna, Serena, Shuldiner, Alan R., Sidney, Steve, Silbernagel, Guenther, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Stancakova, Alena, Sternfeld, Barbara, Swift, Amy J., Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothee, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V., Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Zubair, Niha, Haiman, Christopher A., Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Perusse, Louis, Wilson, James F., Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A., Toenjes, Anke, Bandinelli, Stefania, Palmer, Lyle J., Kardia, Sharon L. R., Rauramaa, Rainer, Sorensen, Thorkild I. A., Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W. J. H., de Geus, Eco J. C., Boomsma, Dorret I., Lehtimaki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G., Kuh, Diana, Liu, Yongmei, Linneberg, Allan, Maerz, Winfried, Strauch, Konstantin, Kivimaki, Mika, Harris, Tamara B., Gudnason, Vilmundur, Voelzke, Henry, Qi, Lu, Jarvelin, Marjo-Riitta, Chambers, John C., Kooner, Jaspal S., Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J., Langenberg, Claudia, Weir, David R., Porteous, David J., Boerwinkle, Eric, Chasman, Daniel I., Abecasis, Goncalo R., Barroso, Ines, McCarthy, Mark I., Frayling, Timothy M., O'Connell, Jeffrey R., van Duijn, Cornelia M., Boehnke, Michael, Heid, Iris M., Mohlke, Karen L., Strachan, David P., Fox, Caroline S., Liu, Ching-Ti, Hirschhorn, Joel N., Klein, Robert J., Johnson, Andrew D., Borecki, Ingrid B., Franks, Paul W., North, Kari E., Cupples, L. Adrienne, Loos, Ruth J. F., and Kilpelainen, Tuomas O.

Abstract

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

Published
2017
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25. Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function

Author

Tang, Wenbo, Kowgier, Matthew, Loth, Daan W., Artigas, Maria Soler, Joubert, Bonnie R., Hodge, Emily, Gharib, Sina A., Smith, Albert V., Ruczinski, Ingo, Gudnason, Vilmundur, Mathias, Rasika A., Harris, Tamara B., Hansel, Nadia N., Launer, Lenore J., Barnes, Kathleen C., Hansen, Joyanna G., Albrecht, Eva, Aldrich, Melinda C., Allerhand, Michael, Barr, R. Graham, Brusselle, Guy G., Couper, David J., Curjuric, Ivan, Davies, Gail, Deary, Ian J., Dupuis, Josee, Fall, Tove, Foy, Millennia, Franceschini, Nora, Gao, Wei, Glaeser, Sven, Gu, Xiangjun, Hancock, Dana B., Heinrich, Joachim, Hofman, Albert, Imboden, Medea, Ingelsson, Erik, James, Alan, Karrasch, Stefan, Koch, Beate, Kritchevsky, Stephen B., Kumar, Ashish, Lahousse, Lies, Li, Guo, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Lohman, Kurt, Lumley, Thomas, McArdle, Wendy L., Meibohm, Bernd, Morris, Andrew P., Morrison, Alanna C., Musk, Bill, North, Kari E., Palmer, Lyle J., Probst-Hensch, Nicole M., Psaty, Bruce M., Rivadeneira, Fernando, Rotter, Jerome I., Schulz, Holger, Smith, Lewis J., Sood, Akshay, Starr, John M., Strachan, David P., Teumer, Alexander, Uitterlinden, Andre G., Voelzke, Henry, Voorman, Arend, Wain, Louise V., Wells, Martin T., Wilk, Jemma B., Williams, O. Dale, Heckbert, Susan R., Stricker, Bruno H., London, Stephanie J., Fornage, Myriam, Tobin, Martin D., O'Connor, George T., Hall, Ian P., Cassano, Patricia A., Tang, Wenbo, Kowgier, Matthew, Loth, Daan W., Artigas, Maria Soler, Joubert, Bonnie R., Hodge, Emily, Gharib, Sina A., Smith, Albert V., Ruczinski, Ingo, Gudnason, Vilmundur, Mathias, Rasika A., Harris, Tamara B., Hansel, Nadia N., Launer, Lenore J., Barnes, Kathleen C., Hansen, Joyanna G., Albrecht, Eva, Aldrich, Melinda C., Allerhand, Michael, Barr, R. Graham, Brusselle, Guy G., Couper, David J., Curjuric, Ivan, Davies, Gail, Deary, Ian J., Dupuis, Josee, Fall, Tove, Foy, Millennia, Franceschini, Nora, Gao, Wei, Glaeser, Sven, Gu, Xiangjun, Hancock, Dana B., Heinrich, Joachim, Hofman, Albert, Imboden, Medea, Ingelsson, Erik, James, Alan, Karrasch, Stefan, Koch, Beate, Kritchevsky, Stephen B., Kumar, Ashish, Lahousse, Lies, Li, Guo, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Lohman, Kurt, Lumley, Thomas, McArdle, Wendy L., Meibohm, Bernd, Morris, Andrew P., Morrison, Alanna C., Musk, Bill, North, Kari E., Palmer, Lyle J., Probst-Hensch, Nicole M., Psaty, Bruce M., Rivadeneira, Fernando, Rotter, Jerome I., Schulz, Holger, Smith, Lewis J., Sood, Akshay, Starr, John M., Strachan, David P., Teumer, Alexander, Uitterlinden, Andre G., Voelzke, Henry, Voorman, Arend, Wain, Louise V., Wells, Martin T., Wilk, Jemma B., Williams, O. Dale, Heckbert, Susan R., Stricker, Bruno H., London, Stephanie J., Fornage, Myriam, Tobin, Martin D., O'Connor, George T., Hall, Ian P., and Cassano, Patricia A.

Abstract

Background: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. Methods: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. Results: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 x 10(-7)). In addition, meta-analysis using the five cohorts with >= 3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18 x 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. Conclusions: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

Published
2014
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26. A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample

Author

Obeidat, Ma'en, Wain, Louise V., Shrine, Nick, Kalsheker, Noor, Artigas, Maria Soler, Repapi, Emmanouela, Burton, Paul R., Johnson, Toby, Ramasamy, Adaikalavan, Zhao, Jing Hua, Zhai, Guangju, Huffman, Jennifer E., Vitart, Veronique, Albrecht, Eva, Igl, Wilmar, Hartikainen, Anna-Liisa, Pouta, Anneli, Cadby, Gemma, Hui, Jennie, Palmer, Lyle J., Hadley, David, McArdle, Wendy L., Rudnicka, Alicja R., Barroso, Ines, Loos, Ruth J. F., Wareham, Nicholas J., Mangino, Massimo, Soranzo, Nicole, Spector, Tim D., Glaeser, Sven, Homuth, Georg, Voelzke, Henry, Deloukas, Panos, Granell, Raquel, Henderson, John, Grkovic, Ivica, Jankovic, Stipan, Zgaga, Lina, Polasek, Ozren, Rudan, Igor, Wright, Alan F., Campbell, Harry, Wild, Sarah H., Wilson, James F., Heinrich, Joachim, Imboden, Medea, Probst-Hensch, Nicole M., Gyllensten, Ulf, Johansson, Åsa, Zaboli, Ghazal, Mustelin, Linda, Rantanen, Taina, Surakka, Ida, Kaprio, Jaakko, Jarvelin, Marjo-Riitta, Hayward, Caroline, Evans, David M., Koch, Beate, Musk, Arthur William, Elliott, Paul, Strachan, David P., Tobin, Martin D., Sayers, Ian, Hall, Ian P., Obeidat, Ma'en, Wain, Louise V., Shrine, Nick, Kalsheker, Noor, Artigas, Maria Soler, Repapi, Emmanouela, Burton, Paul R., Johnson, Toby, Ramasamy, Adaikalavan, Zhao, Jing Hua, Zhai, Guangju, Huffman, Jennifer E., Vitart, Veronique, Albrecht, Eva, Igl, Wilmar, Hartikainen, Anna-Liisa, Pouta, Anneli, Cadby, Gemma, Hui, Jennie, Palmer, Lyle J., Hadley, David, McArdle, Wendy L., Rudnicka, Alicja R., Barroso, Ines, Loos, Ruth J. F., Wareham, Nicholas J., Mangino, Massimo, Soranzo, Nicole, Spector, Tim D., Glaeser, Sven, Homuth, Georg, Voelzke, Henry, Deloukas, Panos, Granell, Raquel, Henderson, John, Grkovic, Ivica, Jankovic, Stipan, Zgaga, Lina, Polasek, Ozren, Rudan, Igor, Wright, Alan F., Campbell, Harry, Wild, Sarah H., Wilson, James F., Heinrich, Joachim, Imboden, Medea, Probst-Hensch, Nicole M., Gyllensten, Ulf, Johansson, Åsa, Zaboli, Ghazal, Mustelin, Linda, Rantanen, Taina, Surakka, Ida, Kaprio, Jaakko, Jarvelin, Marjo-Riitta, Hayward, Caroline, Evans, David M., Koch, Beate, Musk, Arthur William, Elliott, Paul, Strachan, David P., Tobin, Martin D., Sayers, Ian, and Hall, Ian P.

Abstract

Rationale: Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). Objectives: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. Methods: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. Results: The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3 x 10(-5). The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81 x 10(-5)), CNTN5 (P = 4.37 x 10(-4)), and TRPV4 (P = 1.58 x 10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41 x 10(-5)), followed by PDE4D (P = 1.22 x 10(-4)). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38 x 10(-4)), and ESR1 (P = 5.42 x 10(-4)) among ever-smokers. Conclusions: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population.

Published
2011
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27. A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample

Author

University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Department of Public Health, Obeidat, Ma'en, Wain, Louise V., Shrine, Nick, Kalsheker, Noor, Artigas, Maria Soler, Repapi, Emmanouela, Burton, Paul R., Johnson, Toby, Ramasamy, Adaikalavan, Zhao, Jing Hua, Zhai, Guangju, Huffman, Jennifer E., Vitart, Veronique, Albrecht, Eva, Igl, Wilmar, Hartikainen, Anna-Liisa, Pouta, Anneli, Cadby, Gemma, Hui, Jennie, Palmer, Lyle J., Hadley, David, McArdle, Wendy L., Rudnicka, Alicja R., Barroso, Ines, Loos, Ruth J. F., Wareham, Nicholas J., Mangino, Massimo, Soranzo, Nicole, Spector, Tim D., Glaeser, Sven, Homuth, Georg, Voelzke, Henry, Deloukas, Panos, Granell, Raquel, Henderson, John, Grkovic, Ivica, Jankovic, Stipan, Zgaga, Lina, Polasek, Ozren, Rudan, Igor, Wright, Alan F., Campbell, Harry, Wild, Sarah H., Wilson, James F., Heinrich, Joachim, Imboden, Medea, Probst-Hensch, Nicole M., Gyllensten, Ulf, Johansson, Asa, Zaboli, Ghazal, Mustelin, Linda, Rantanen, Taina, Surakka, Ida, Kaprio, Jaakko, Jarvelin, Marjo-Riitta, Hayward, Caroline, Evans, David M., Koch, Beate, Musk, Arthur William, Elliott, Paul, Strachan, David P., Tobin, Martin D., Sayers, Ian, Hall, Ian P., SpiroMeta Consortium, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Department of Public Health, Obeidat, Ma'en, Wain, Louise V., Shrine, Nick, Kalsheker, Noor, Artigas, Maria Soler, Repapi, Emmanouela, Burton, Paul R., Johnson, Toby, Ramasamy, Adaikalavan, Zhao, Jing Hua, Zhai, Guangju, Huffman, Jennifer E., Vitart, Veronique, Albrecht, Eva, Igl, Wilmar, Hartikainen, Anna-Liisa, Pouta, Anneli, Cadby, Gemma, Hui, Jennie, Palmer, Lyle J., Hadley, David, McArdle, Wendy L., Rudnicka, Alicja R., Barroso, Ines, Loos, Ruth J. F., Wareham, Nicholas J., Mangino, Massimo, Soranzo, Nicole, Spector, Tim D., Glaeser, Sven, Homuth, Georg, Voelzke, Henry, Deloukas, Panos, Granell, Raquel, Henderson, John, Grkovic, Ivica, Jankovic, Stipan, Zgaga, Lina, Polasek, Ozren, Rudan, Igor, Wright, Alan F., Campbell, Harry, Wild, Sarah H., Wilson, James F., Heinrich, Joachim, Imboden, Medea, Probst-Hensch, Nicole M., Gyllensten, Ulf, Johansson, Asa, Zaboli, Ghazal, Mustelin, Linda, Rantanen, Taina, Surakka, Ida, Kaprio, Jaakko, Jarvelin, Marjo-Riitta, Hayward, Caroline, Evans, David M., Koch, Beate, Musk, Arthur William, Elliott, Paul, Strachan, David P., Tobin, Martin D., Sayers, Ian, Hall, Ian P., and SpiroMeta Consortium

Abstract

RATIONALE: Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). OBJECTIVES: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. METHODS: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. RESULTS: The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV(1) or FEV(1)/FVC traits using a carefully defined significance threshold of 1.3×10(-5). The most significant loci associated with FEV(1) include SNPs tagging MACROD2 (P = 6.81×10(-5)), CNTN5 (P = 4.37×10(-4)), and TRPV4 (P = 1.58×10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV(1) (P = 8.41×10(-5)), followed by PDE4D (P = 1.22×10(-4)). The strongest association with FEV(1)/FVC ratio was observed with ABCC1 (P = 4.38×10(-4)), and ESR1 (P = 5.42×10(-4)) among ever-smokers. CONCLUSIONS: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV(1) among smokers in the general population.

Published
2011

28. Genome-wide association study identifies five loci associated with lung function

Author

Repapi, Emmanouela, Sayers, Ian, Wain, Louise V., Burton, Paul R., Johnson, Toby, Obeidat, Ma'en, Zhao, Jing Hua, Ramasamy, Adaikalavan, Zhai, Guangju, Vitart, Veronique, Huffman, Jennifer E., Igl, Wilmar, Albrecht, Eva, Deloukas, Panos, Henderson, John, Granell, Raquel, McArdle, Wendy L., Rudnicka, Alicja R., Barroso, Ines, Loos, Ruth J. F., Wareham, Nicholas J., Mustelin, Linda, Rantanen, Taina, Surakka, Ida, Imboden, Medea, Wichmann, H. Erich, Grkovic, Ivica, Jankovic, Stipan, Zgaga, Lina, Hartikainen, Anna-Liisa, Peltonen, Leena, Gyllensten, Ulf, Johansson, Åsa, Zaboli, Ghazal, Campbell, Harry, Wild, Sarah H., Wilson, James F., Glaeser, Sven, Homuth, Georg, Voelzke, Henry, Mangino, Massimo, Soranzo, Nicole, Spector, Tim D., Polasek, Ozren, Rudan, Igor, Wright, Alan F., Heliovaara, Markku, Ripatti, Samuli, Pouta, Anneli, Naluai, Asa Torinsson, Olin, Anna-Carin, Torén, Kjell, Cooper, Matthew N., James, Alan L., Palmer, Lyle J., Hingorani, Aroon D., Wannamethee, S. Goya, Whincup, Peter H., Smith, George Davey, Ebrahim, Shah, McKeever, Tricia M., Pavord, Ian D., MacLeod, Andrew K., Morris, Andrew D., Porteous, David J., Cooper, Cyrus, Dennison, Elaine, Shaheen, Seif, Karrasch, Stefan, Schnabel, Eva, Schulz, Holger, Grallert, Harald, Bouatia-Naji, Nabila, Delplanque, Jerome, Froguel, Philippe, Blakey, John D., Britton, John R., Morris, Richard W., Holloway, John W., Lawlor, Debbie A., Hui, Jennie, Nyberg, Fredrik, Jarvelin, Marjo-Riitta, Jackson, Cathy, Kahonen, Mika, Kaprio, Jaakko, Probst-Hensch, Nicole M., Koch, Beate, Hayward, Caroline, Evans, David M., Elliott, Paul, Strachan, David P., Hall, Ian P., Tobin, Martin D., Repapi, Emmanouela, Sayers, Ian, Wain, Louise V., Burton, Paul R., Johnson, Toby, Obeidat, Ma'en, Zhao, Jing Hua, Ramasamy, Adaikalavan, Zhai, Guangju, Vitart, Veronique, Huffman, Jennifer E., Igl, Wilmar, Albrecht, Eva, Deloukas, Panos, Henderson, John, Granell, Raquel, McArdle, Wendy L., Rudnicka, Alicja R., Barroso, Ines, Loos, Ruth J. F., Wareham, Nicholas J., Mustelin, Linda, Rantanen, Taina, Surakka, Ida, Imboden, Medea, Wichmann, H. Erich, Grkovic, Ivica, Jankovic, Stipan, Zgaga, Lina, Hartikainen, Anna-Liisa, Peltonen, Leena, Gyllensten, Ulf, Johansson, Åsa, Zaboli, Ghazal, Campbell, Harry, Wild, Sarah H., Wilson, James F., Glaeser, Sven, Homuth, Georg, Voelzke, Henry, Mangino, Massimo, Soranzo, Nicole, Spector, Tim D., Polasek, Ozren, Rudan, Igor, Wright, Alan F., Heliovaara, Markku, Ripatti, Samuli, Pouta, Anneli, Naluai, Asa Torinsson, Olin, Anna-Carin, Torén, Kjell, Cooper, Matthew N., James, Alan L., Palmer, Lyle J., Hingorani, Aroon D., Wannamethee, S. Goya, Whincup, Peter H., Smith, George Davey, Ebrahim, Shah, McKeever, Tricia M., Pavord, Ian D., MacLeod, Andrew K., Morris, Andrew D., Porteous, David J., Cooper, Cyrus, Dennison, Elaine, Shaheen, Seif, Karrasch, Stefan, Schnabel, Eva, Schulz, Holger, Grallert, Harald, Bouatia-Naji, Nabila, Delplanque, Jerome, Froguel, Philippe, Blakey, John D., Britton, John R., Morris, Richard W., Holloway, John W., Lawlor, Debbie A., Hui, Jennie, Nyberg, Fredrik, Jarvelin, Marjo-Riitta, Jackson, Cathy, Kahonen, Mika, Kaprio, Jaakko, Probst-Hensch, Nicole M., Koch, Beate, Hayward, Caroline, Evans, David M., Elliott, Paul, Strachan, David P., Hall, Ian P., and Tobin, Martin D.

Abstract

Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 10−15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

Published
2010
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30. Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function

Author

Hancock, Dana B., Artigas, María Soler, Gharib, Sina A., Henry, Amanda, Manichaikul, Ani, Ramasamy, Adaikalavan, Loth, Daan W., Imboden, Medea, Koch, Beate, McArdle, Wendy L., Smith, Albert V., Smolonska, Joanna, Sood, Akshay, Tang, Wenbo, Zhai, Guangju, Burkart, Kristin M., Curjuric, Ivan, Eijgelsheim, Mark, Elliott, Paul, Gu, Xiangjun, Harris, Tamara B., Janson, Christer, Homuth, Georg, Hysi, Pirro G., Loehr, Laura R., Lohman, Kurt, Loos, Ruth J. F., Marciante, Kristin D., Obeidat, Ma'en, Postma, Dirkje S., Aldrich, Melinda C., Brusselle, Guy G., Eiriksdottir, Gudny, Franceschini, Nora, Heinrich, Joachim, Rotter, Jerome I., Wijmenga, Cisca, Bentley, Amy R., Laurie, Cathy C., Lumley, Thomas, Morrison, Alanna C., Joubert, Bonnie R., Rivadeneira, Fernando, Couper, David J., Kritchevsky, Stephen B., Liu, Yongmei, Wjst, Matthias, Wain, Louise V., Vonk, Judith M., Uitterlinden, André G., Rochat, Thierry, Rich, Stephen S., Psaty, Bruce M., O'Connor, George T., North, Kari E., Mirel, Daniel B., Meibohm, Bernd, Launer, Lenore J., Khaw, Kay-Tee, Hartikainen, Anna-Liisa, Hammond, Christopher J., Gläser, Sven, Marchini, Jonathan, Wareham, Nicholas J., Völzke, Henry, Stricker, Bruno H. C., Spector, Timothy D., Probst-Hensch, Nicole M., Jarvis, Deborah, Jarvelin, Marjo-Riitta, Heckbert, Susan R., Gudnason, Vilmundur, Boezen, H. Marike, Barr, R. Graham, Cassano, Patricia A., Strachan, David P., Fornage, Myriam, Hall, Ian P., Dupuis, Josée, Tobin, Martin D., London, Stephanie J., Wilk, Jemma, Zhao, Jing Hua, Aschard, Hugues, Liu, Jason Z., Manning, Alisa, Chen, Ting-Hsu, Williams, O. Dale, Kraft, Phillip, and Hofman, Albert

Subjects
Biology, Genetics, Human Genetics, Genetic Association Studies, Genome-Wide Association Studies, Genetics of Disease, Genomics, Genome Analysis Tools, Genome Scans, Medicine, Epidemiology, Genetic Epidemiology, Public Health, Environmental Health, Pulmonology, Smoking Related Disorders
Abstract

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second \((FEV_1)\), and its ratio to forced vital capacity \((FEV_1/FVC)\). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on \(FEV_1\) and \(FEV_1/FVC\) across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest \(P_{JMA} = 5.00×10^{−11})\), HLA-DQB1 and HLA-DQA2 (smallest \(P_{JMA} = 4.35×10^{−9})\), and KCNJ2 and SOX9 (smallest \(P_{JMA} = 1.28×10^{−8})\) were associated with \(FEV_1/FVC\) or \(FEV_1\) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects., Version of Record

Published
2012
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