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Genetic Associations and Architecture of Asthma-COPD Overlap

BACKGROUND: Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. RESEARCH QUESTION: What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for ast...

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Autores principales: John, Catherine, Guyatt, Anna L., Shrine, Nick, Packer, Richard, Olafsdottir, Thorunn A., Liu, Jiangyuan, Hayden, Lystra P., Chu, Su H., Koskela, Jukka T., Luan, Jian’an, Li, Xingnan, Terzikhan, Natalie, Xu, Hanfei, Bartz, Traci M., Petersen, Hans, Leng, Shuguang, Belinsky, Steven A., Cepelis, Aivaras, Hernández Cordero, Ana I., Obeidat, Ma’en, Thorleifsson, Gudmar, Meyers, Deborah A., Bleecker, Eugene R., Sakoda, Lori C., Iribarren, Carlos, Tesfaigzi, Yohannes, Gharib, Sina A., Dupuis, Josée, Brusselle, Guy, Lahousse, Lies, Ortega, Victor E., Jonsdottir, Ingileif, Sin, Don D., Bossé, Yohan, van den Berge, Maarten, Nickle, David, Quint, Jennifer K., Sayers, Ian, Hall, Ian P., Langenberg, Claudia, Ripatti, Samuli, Laitinen, Tarja, Wu, Ann C., Lasky-Su, Jessica, Bakke, Per, Gulsvik, Amund, Hersh, Craig P., Hayward, Caroline, Langhammer, Arnulf, Brumpton, Ben, Stefansson, Kari, Cho, Michael H., Wain, Louise V., Tobin, Martin D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American College of Chest Physicians 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131047/
https://www.ncbi.nlm.nih.gov/pubmed/35104449
http://dx.doi.org/10.1016/j.chest.2021.12.674
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author John, Catherine
Guyatt, Anna L.
Shrine, Nick
Packer, Richard
Olafsdottir, Thorunn A.
Liu, Jiangyuan
Hayden, Lystra P.
Chu, Su H.
Koskela, Jukka T.
Luan, Jian’an
Li, Xingnan
Terzikhan, Natalie
Xu, Hanfei
Bartz, Traci M.
Petersen, Hans
Leng, Shuguang
Belinsky, Steven A.
Cepelis, Aivaras
Hernández Cordero, Ana I.
Obeidat, Ma’en
Thorleifsson, Gudmar
Meyers, Deborah A.
Bleecker, Eugene R.
Sakoda, Lori C.
Iribarren, Carlos
Tesfaigzi, Yohannes
Gharib, Sina A.
Dupuis, Josée
Brusselle, Guy
Lahousse, Lies
Ortega, Victor E.
Jonsdottir, Ingileif
Sin, Don D.
Bossé, Yohan
van den Berge, Maarten
Nickle, David
Quint, Jennifer K.
Sayers, Ian
Hall, Ian P.
Langenberg, Claudia
Ripatti, Samuli
Laitinen, Tarja
Wu, Ann C.
Lasky-Su, Jessica
Bakke, Per
Gulsvik, Amund
Hersh, Craig P.
Hayward, Caroline
Langhammer, Arnulf
Brumpton, Ben
Stefansson, Kari
Cho, Michael H.
Wain, Louise V.
Tobin, Martin D.
author_facet John, Catherine
Guyatt, Anna L.
Shrine, Nick
Packer, Richard
Olafsdottir, Thorunn A.
Liu, Jiangyuan
Hayden, Lystra P.
Chu, Su H.
Koskela, Jukka T.
Luan, Jian’an
Li, Xingnan
Terzikhan, Natalie
Xu, Hanfei
Bartz, Traci M.
Petersen, Hans
Leng, Shuguang
Belinsky, Steven A.
Cepelis, Aivaras
Hernández Cordero, Ana I.
Obeidat, Ma’en
Thorleifsson, Gudmar
Meyers, Deborah A.
Bleecker, Eugene R.
Sakoda, Lori C.
Iribarren, Carlos
Tesfaigzi, Yohannes
Gharib, Sina A.
Dupuis, Josée
Brusselle, Guy
Lahousse, Lies
Ortega, Victor E.
Jonsdottir, Ingileif
Sin, Don D.
Bossé, Yohan
van den Berge, Maarten
Nickle, David
Quint, Jennifer K.
Sayers, Ian
Hall, Ian P.
Langenberg, Claudia
Ripatti, Samuli
Laitinen, Tarja
Wu, Ann C.
Lasky-Su, Jessica
Bakke, Per
Gulsvik, Amund
Hersh, Craig P.
Hayward, Caroline
Langhammer, Arnulf
Brumpton, Ben
Stefansson, Kari
Cho, Michael H.
Wain, Louise V.
Tobin, Martin D.
author_sort John, Catherine
collection PubMed
description BACKGROUND: Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. RESEARCH QUESTION: What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma? STUDY DESIGN AND METHODS: We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P < 5 × 10(–6)) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2). RESULTS: We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P < 5 × 10(–8)) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent. INTERPRETATION: We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma.
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spelling pubmed-91310472022-06-04 Genetic Associations and Architecture of Asthma-COPD Overlap John, Catherine Guyatt, Anna L. Shrine, Nick Packer, Richard Olafsdottir, Thorunn A. Liu, Jiangyuan Hayden, Lystra P. Chu, Su H. Koskela, Jukka T. Luan, Jian’an Li, Xingnan Terzikhan, Natalie Xu, Hanfei Bartz, Traci M. Petersen, Hans Leng, Shuguang Belinsky, Steven A. Cepelis, Aivaras Hernández Cordero, Ana I. Obeidat, Ma’en Thorleifsson, Gudmar Meyers, Deborah A. Bleecker, Eugene R. Sakoda, Lori C. Iribarren, Carlos Tesfaigzi, Yohannes Gharib, Sina A. Dupuis, Josée Brusselle, Guy Lahousse, Lies Ortega, Victor E. Jonsdottir, Ingileif Sin, Don D. Bossé, Yohan van den Berge, Maarten Nickle, David Quint, Jennifer K. Sayers, Ian Hall, Ian P. Langenberg, Claudia Ripatti, Samuli Laitinen, Tarja Wu, Ann C. Lasky-Su, Jessica Bakke, Per Gulsvik, Amund Hersh, Craig P. Hayward, Caroline Langhammer, Arnulf Brumpton, Ben Stefansson, Kari Cho, Michael H. Wain, Louise V. Tobin, Martin D. Chest Asthma: Original Research BACKGROUND: Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. RESEARCH QUESTION: What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma? STUDY DESIGN AND METHODS: We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P < 5 × 10(–6)) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2). RESULTS: We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P < 5 × 10(–8)) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent. INTERPRETATION: We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma. American College of Chest Physicians 2022-05 2022-01-31 /pmc/articles/PMC9131047/ /pubmed/35104449 http://dx.doi.org/10.1016/j.chest.2021.12.674 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Asthma: Original Research
John, Catherine
Guyatt, Anna L.
Shrine, Nick
Packer, Richard
Olafsdottir, Thorunn A.
Liu, Jiangyuan
Hayden, Lystra P.
Chu, Su H.
Koskela, Jukka T.
Luan, Jian’an
Li, Xingnan
Terzikhan, Natalie
Xu, Hanfei
Bartz, Traci M.
Petersen, Hans
Leng, Shuguang
Belinsky, Steven A.
Cepelis, Aivaras
Hernández Cordero, Ana I.
Obeidat, Ma’en
Thorleifsson, Gudmar
Meyers, Deborah A.
Bleecker, Eugene R.
Sakoda, Lori C.
Iribarren, Carlos
Tesfaigzi, Yohannes
Gharib, Sina A.
Dupuis, Josée
Brusselle, Guy
Lahousse, Lies
Ortega, Victor E.
Jonsdottir, Ingileif
Sin, Don D.
Bossé, Yohan
van den Berge, Maarten
Nickle, David
Quint, Jennifer K.
Sayers, Ian
Hall, Ian P.
Langenberg, Claudia
Ripatti, Samuli
Laitinen, Tarja
Wu, Ann C.
Lasky-Su, Jessica
Bakke, Per
Gulsvik, Amund
Hersh, Craig P.
Hayward, Caroline
Langhammer, Arnulf
Brumpton, Ben
Stefansson, Kari
Cho, Michael H.
Wain, Louise V.
Tobin, Martin D.
Genetic Associations and Architecture of Asthma-COPD Overlap
title Genetic Associations and Architecture of Asthma-COPD Overlap
title_full Genetic Associations and Architecture of Asthma-COPD Overlap
title_fullStr Genetic Associations and Architecture of Asthma-COPD Overlap
title_full_unstemmed Genetic Associations and Architecture of Asthma-COPD Overlap
title_short Genetic Associations and Architecture of Asthma-COPD Overlap
title_sort genetic associations and architecture of asthma-copd overlap
topic Asthma: Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131047/
https://www.ncbi.nlm.nih.gov/pubmed/35104449
http://dx.doi.org/10.1016/j.chest.2021.12.674
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