Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

Sakornsakolpat, Phuwanat; Prokopenko, Dmitry; Lamontagne, Maxime; Reeve, Nicola F.; Guyatt, Anna L.; Jackson, Victoria E.; Shrine, Nick; Qiao, Dandi; Bartz, Traci M.; Kim, Deog Kyeom; Lee, Mi Kyeong; Latourelle, Jeanne C.; Li, Xingnan; Morrow, Jarrett D.; Obeidat, Ma’en; Wyss, Annah B.; Bakke, Per; Barr, R. Graham; Beaty, Terri H.; Belinsky, Steven A.; Brusselle, Guy G.; Crapo, James D.; de Jong, Kim; DeMeo, Dawn L.; Fingerlin, Tasha E.; Gharib, Sina A.; Gulsvik, Amund; Hall, Ian P.; Hokanson, John E.; Kim, Woo Jin; Lomas, David A.; London, Stephanie J.; Meyers, Deborah A.; O’Connor, George T.; Rennard, Stephen I.; Schwartz, David A.; Sliwinski, Pawel; Sparrow, David; Strachan, David P.; Tal-Singer, Ruth; Tesfaigzi, Yohannes; Vestbo, Jørgen; Vonk, Judith M.; Yim, Jae-Joon; Zhou, Xiaobo; Bossé, Yohan; Manichaikul, Ani; Lahousse, Lies; Silverman, Edwin K.; Boezen, H. Marike

doi:10.1038/s41588-018-0342-2

Cited by 384

The DOI matches its Crossref record; 139 of the 139 references it cites were found in a registry or an index.

Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

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Sakornsakolpat, Phuwanat, Prokopenko, Dmitry, Lamontagne, Maxime, Reeve, Nicola F., Guyatt, Anna L., Jackson, Victoria E., Shrine, Nick, Qiao, Dandi, Bartz, Traci M., Kim, Deog Kyeom, Lee, Mi Kyeong, Latourelle, Jeanne C., Li, Xingnan, Morrow, Jarrett D., Obeidat, Ma’en, Wyss, Annah B., Bakke, Per, Barr, R. Graham, Beaty, Terri H., Belinsky, Steven A., Brusselle, Guy G., Crapo, James D., de Jong, Kim, DeMeo, Dawn L., Fingerlin, Tasha E., Gharib, Sina A., Gulsvik, Amund, Hall, Ian P., Hokanson, John E., Kim, Woo Jin, Lomas, David A., London, Stephanie J., Meyers, Deborah A., O’Connor, George T., Rennard, Stephen I., Schwartz, David A., Sliwinski, Pawel, Sparrow, David, Strachan, David P., Tal-Singer, Ruth, Tesfaigzi, Yohannes, Vestbo, Jørgen, Vonk, Judith M., Yim, Jae-Joon, Zhou, Xiaobo, Bossé, Yohan, Manichaikul, Ani, Lahousse, Lies, Silverman, Edwin K., Boezen, H. Marike, Wain, Louise V., Tobin, Martin D., Hobbs, Brian D., Cho, Michael H., SpiroMeta Consortium, Shrine, Nick, Guyatt, Anna L., Batini, Chiara, Zhao, Jing Hua, Wielscher, Matthias, Understanding Society Scientific Group, Weiss, Stefan, Kentistou, Katherine A., Cook, James P., Hui, Jennie, Karrasch, Stefan, Imboden, Medea, Harris, Sarah E., Marten, Jonathan, Enroth, Stefan, Kerr, Shona M., Surakka, Ida, Vitart, Veronique, Lehtimäki, Terho, Ewert, Ralf, Gieger, Christian, Homuth, Georg, Joshi, Peter K., Langenberg, Claudia, Lind, Lars, Luan, Jian’an, Mahajan, Anubha, Murray, Alison, Porteous, David J., Rawal, Rajesh, Smith, Blair H., Timmers, Paul R. H. J., Raitakari, Olli T., Kähönen, Mika, Polasek, Ozren, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Probst-Hensch, Nicole M., Schulz, Holger, James, Alan L., Wilson, James F., Stubbe, Beate, Zeggini, Eleftheria, Jarvelin, Marjo-Riitta, Wareham, Nick, Hayward, Caroline, Morris, Andrew P., Strachan, David P., Hall, Ian P., Tobin, Martin D., Wain, Louise V., International COPD Genetics Consortium, Agusti, Alvar, Anderson, Wayne, Bakerly, Nawar, Bakke, Per, Bals, Robert, Barnes, Kathleen C., Barr, R. Graham, Beaty, Terri H., Bleecker, Eugene R., Boezen, H. Marike, Bossé, Yohan, Bowler, Russell, Brightling, Christopher, de Bruijne, Marleen, Castaldi, Peter J., Celli, Bartolome, Cho, Michael H., Coxson, Harvey O., Crapo, James D., Crystal, Ron, de Jong, Pim, Dirksen, Asger, Dy, Jennifer, Foreman, Marilyn, Garcia-Aymerich, Judith, Gevenois, Pierre, Ghosh, Soumitra, Gietema, Hester, Gulsvik, Amund, Hall, Ian P., Hansel, Nadia, Hersh, Craig P., Hobbs, Brian D., Hoffman, Eric, Kalsheker, Noor, Kauczor, Hans-Ulrich, Kim, Woo Jin, Kim, Deog Kyeom, Laitinen, Tarja, Lambrechts, Diether, Lee, Sang-Do, Litonjua, Augusto A., Lomas, David A., London, Stephanie J., Loth, Daan W., Lutz, Sharon M., Lynch, David, MacNee, William, McDonald, Merry-Lynn, Meyers, Deborah A., Newell, John D., Nordestgaard, Borge G., O’Connor, George T., Obeidat, Ma’en, Oh, Yeon-Mok, Paré, Peter D., Pistolesi, Massimo, Postma, Dirkje S., Puhan, Milo, Regan, Elizabeth, Rich, Stephen S., Seo, Joon Beom, Short, Andrea, Silverman, Edwin K., Sparrow, David, Stoel, Berend, Strachan, David P., Sverzellati, Nicola, Tal-Singer, Ruth, ter Riet, Gerben, Tesfaigzi, Yohannes, Tobin, Martin D., Van Beek, Edwin J. R., van Ginneken, Bram, Vestbo, Jørgen, Vogelmeier, Claus F., Wain, Louise V., Wanner, Adam, Washko, George, Wauters, Els, Wouters, Emiel F. M., Young, Robert P., Zeigler-Heitbrock, Loems·2019·Nature Genetics

DOI 10.1038/s41588-018-0342-2

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Abstract

Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10−8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD. Genome-wide analysis of chronic obstructive pulmonary disease identifies 82 loci, 35 of which are new. Integration of gene expression and genomic annotation data shows enrichment of signals in lung tissue, smooth muscle and several lung cell types.

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Authors: Sakornsakolpat, P., Prokopenko, D., Lamontagne, M., Reeve, N. F., Guyatt, A. L., Jackson, V. E., Shrine, N., Qiao, D., Bartz, T. M., Kim, D. K., Lee, M. K., Latourelle, J. C., Li, X., Morrow, J. D., Obeidat, M., Wyss, A. B., Bakke, P., Barr, R. G., Beaty, T. H., Belinsky, S. A., Brusselle, G. G., Crapo, J. D., de Jong, K., DeMeo, D. L., Fingerlin, T. E., Gharib, S. A., Gulsvik, A., Hall, I. P., Hokanson, J. E., Kim, W. J., Lomas, D. A., London, S. J., Meyers, D. A., O’Connor, G. T., Rennard, S. I., Schwartz, D. A., Sliwinski, P., Sparrow, D., Strachan, D. P., Tal-Singer, R., Tesfaigzi, Y., Vestbo, J., Vonk, J. M., Yim, J.-J., Zhou, X., Bossé, Y., Manichaikul, A., Lahousse, L., Silverman, E. K., Boezen, H. M., Wain, L. V., Tobin, M. D., Hobbs, B. D., Cho, M. H., SpiroMeta Consortium, Shrine, N., Guyatt, A. L., Batini, C., Zhao, J. H., Wielscher, M., Understanding Society Scientific Group, Weiss, S., Kentistou, K. A., Cook, J. P., Hui, J., Karrasch, S., Imboden, M., Harris, S. E., Marten, J., Enroth, S., Kerr, S. M., Surakka, I., Vitart, V., Lehtimäki, T., Ewert, R., Gieger, C., Homuth, G., Joshi, P. K., Langenberg, C., Lind, L., Luan, J., Mahajan, A., Murray, A., Porteous, D. J., Rawal, R., Smith, B. H., Timmers, P. R. H. J., Raitakari, O. T., Kähönen, M., Polasek, O., Gyllensten, U., Rudan, I., Deary, I. J., Probst-Hensch, N. M., Schulz, H., James, A. L., Wilson, J. F., Stubbe, B., Zeggini, E., Jarvelin, M.-R., Wareham, N., Hayward, C., Morris, A. P., Strachan, D. P., Hall, I. P., Tobin, M. D., Wain, L. V., International COPD Genetics Consortium, Agusti, A., Anderson, W., Bakerly, N., Bakke, P., Bals, R., Barnes, K. C., Barr, R. G., Beaty, T. H., Bleecker, E. R., Boezen, H. M., Bossé, Y., Bowler, R., Brightling, C., de Bruijne, M., Castaldi, P. J., Celli, B., Cho, M. H., Coxson, H. O., Crapo, J. D., Crystal, R., de Jong, P., Dirksen, A., Dy, J., Foreman, M., Garcia-Aymerich, J., Gevenois, P., Ghosh, S., Gietema, H., Gulsvik, A., Hall, I. P., Hansel, N., Hersh, C. P., Hobbs, B. D., Hoffman, E., Kalsheker, N., Kauczor, H.-U., Kim, W. J., Kim, D. K., Laitinen, T., Lambrechts, D., Lee, S.-D., Litonjua, A. A., Lomas, D. A., London, S. J., Loth, D. W., Lutz, S. M., Lynch, D., MacNee, W., McDonald, M.-L., Meyers, D. A., Newell, J. D., Nordestgaard, B. G., O’Connor, G. T., Obeidat, M., Oh, Y.-M., Paré, P. D., Pistolesi, M., Postma, D. S., Puhan, M., Regan, E., Rich, S. S., Seo, J. B., Short, A., Silverman, E. K., Sparrow, D., Stoel, B., Strachan, D. P., Sverzellati, N., Tal-Singer, R., ter Riet, G., Tesfaigzi, Y., Tobin, M. D., Van Beek, E. J. R., van Ginneken, B., Vestbo, J., Vogelmeier, C. F., Wain, L. V., Wanner, A., Washko, G., Wauters, E., Wouters, E. F. M., Young, R. P., & Zeigler-Heitbrock, L.
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2019-02-25
Volume: 51
Issue: 3
Pages: 494-505
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/s41588-018-0342-2
OpenAlex: W2917263971
Cited by: 384
References: 139
FWCI: 32.62
Type: journal article
Language: en
Open access: hybrid

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The paper: Sakornsakolpat, P., Prokopenko, D., Lamontagne, M., Reeve, N. F., Guyatt, A. L., Jackson, V. E., Shrine, N., Qiao, D., Bartz, T. M., Kim, D. K., Lee, M. K., Latourelle, J. C., Li, X., Morrow, J. D., Obeidat, M., Wyss, A. B., Bakke, P., Barr, R. G., Beaty, T. H., . . . Zeigler-Heitbrock, L. (2019). Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations. Nature Genetics. https://doi.org/10.1038/s41588-018-0342-2

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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

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