151. Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- Author
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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., Batini, Chiara, Zhao, Jing Hua, Wielscher, Matthias, 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., Agusti, Alvar, Anderson, Wayne, Bakerly, Nawar, Bals, Robert, Barnes, Kathleen C., Bleecker, Eugene R., Bowler, Russell, Brightling, Christopher, de Bruijne, Marleen, Castaldi, Peter J., Celli, Bartolome, Coxson, Harvey O., Crystal, Ron, de Jong, Pim, Dirksen, Asger, Dy, Jennifer, Foreman, Marilyn, Garcia-Aymerich, Judith, Gevenois, Pierre, Ghosh, Soumitra, Gietema, Hester, Hansel, Nadia, Hersh, Craig P., Hoffman, Eric, Kalsheker, Noor, Kauczor, Hans-Ulrich, Laitinen, Tarja, Lambrechts, Diether, Lee, Sang-Do, Litonjua, Augusto A., Loth, Daan W., Lutz, Sharon M., Lynch, David, MacNee, William, McDonald, Merry-Lynn, Newell, John D., Nordestgaard, Borge G., Oh, Yeon-Mok, Paré, Peter D., Pistolesi, Massimo, Postma, Dirkje S., Puhan, Milo, Regan, Elizabeth, Rich, Stephen S., Seo, Joon Beom, Short, Andrea, Stoel, Berend, Sverzellati, Nicola, ter Riet, Gerben, Van Beek, Edwin J. R., van Ginneken, Bram, Vogelmeier, Claus F., Wanner, Adam, Washko, George, Wauters, Els, Wouters, Emiel F. M., Young, Robert P., Zeigler-Heitbrock, Loems, SpiroMeta Consortium, Understanding Society Scientific Group, International COPD Genetics Consortium, Institute for Molecular Medicine Finland, Groningen Research Institute for Asthma and COPD (GRIAC), Life Course Epidemiology (LCE), Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), MUMC+: MA Longziekten (3), RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie, General practice, APH - Aging & Later Life, APH - Personalized Medicine, ACS - Diabetes & metabolism, Epidemiology, Pulmonary Medicine, Medical Informatics, and Radiology & Nuclear Medicine
- Subjects
Male ,Lydia Becker Institute ,Pulmonary Fibrosis ,LD SCORE REGRESSION ,Gene Expression ,Genome-wide association study ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Pulmonary fibrosis ,GWAS ,Lung ,GENOME-WIDE ASSOCIATION ,ACIDIC-MAMMALIAN-CHITINASE ,LUNG-FUNCTION ,EXTRACELLULAR-MATRIX ,PREDOMINANT EMPHYSEMA ,CONNECTIVITY MAP ,ATOPIC ASTHMA ,RISK LOCI ,0303 health sciences ,COPD ,education.field_of_study ,Smoking ,1184 Genetics, developmental biology, physiology ,Middle Aged ,3. Good health ,Phenotype ,medicine.anatomical_structure ,Medical genetics ,Female ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,Adult ,medicine.medical_specialty ,Population ,Biology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation ,Genetics ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,education ,Aged ,030304 developmental biology ,Asthma ,medicine.disease ,respiratory tract diseases ,Genetic Loci ,Case-Control Studies ,Immunology ,3111 Biomedicine ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide novel 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 with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function. Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified enrichment for 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 of quantitative imaging features and comorbidity associations. Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD., Editorial summary 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.
- Published
- 2019