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Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study

Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD); however, more than 25% of COPD patients are non-smokers, and gene-by-smoking interactions are expected to affect COPD onset. We aimed to identify the common genetic variants interacting with pack-years of smoking on FEV...

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Autores principales: Park, Boram, An, Jaehoon, Kim, Wonji, Kang, Hae Yeon, Koh, Sang Baek, Oh, Bermseok, Jung, Keum Ji, Jee, Sun Ha, Kim, Woo Jin, Cho, Michael H., Silverman, Edwin K., Park, Taesung, Won, Sungho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403370/
https://www.ncbi.nlm.nih.gov/pubmed/32753590
http://dx.doi.org/10.1038/s41598-020-70092-0
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author Park, Boram
An, Jaehoon
Kim, Wonji
Kang, Hae Yeon
Koh, Sang Baek
Oh, Bermseok
Jung, Keum Ji
Jee, Sun Ha
Kim, Woo Jin
Cho, Michael H.
Silverman, Edwin K.
Park, Taesung
Won, Sungho
author_facet Park, Boram
An, Jaehoon
Kim, Wonji
Kang, Hae Yeon
Koh, Sang Baek
Oh, Bermseok
Jung, Keum Ji
Jee, Sun Ha
Kim, Woo Jin
Cho, Michael H.
Silverman, Edwin K.
Park, Taesung
Won, Sungho
author_sort Park, Boram
collection PubMed
description Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD); however, more than 25% of COPD patients are non-smokers, and gene-by-smoking interactions are expected to affect COPD onset. We aimed to identify the common genetic variants interacting with pack-years of smoking on FEV(1)/FVC ratios in individuals with normal lung function. A genome-wide interaction study (GWIS) on FEV(1)/FVC was performed for individuals with FEV(1)/FVC ratio ≥ 70 in the Korea Associated Resource cohort data, and significant SNPs were validated using data from two other Korean cohorts. The GWIS revealed that rs10947231 and rs8192575 met genome-wide significant levels; For [Formula: see text] the likelihood ratio (LR) test was conducted, and its P values, P(LR), for rs10947231 and rs8192575 were 2.23 × 10(–12) and 1.18 × 10(–8), respectively. Interaction between rs8192575 and smoking is significantly replicated with two additional data (P(INT) = 0.0454, 0.0131). Expression quantitative trait loci, topologically associated domains, and PrediXcan analyses revealed that rs8192575 is significantly associated with AGER expression. SNPs on the 6p21 region are associated with FEV(1)/FVC, and the effect of smoking on FEV(1)/FVC differs among the associated genotypes.
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spelling pubmed-74033702020-08-07 Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study Park, Boram An, Jaehoon Kim, Wonji Kang, Hae Yeon Koh, Sang Baek Oh, Bermseok Jung, Keum Ji Jee, Sun Ha Kim, Woo Jin Cho, Michael H. Silverman, Edwin K. Park, Taesung Won, Sungho Sci Rep Article Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD); however, more than 25% of COPD patients are non-smokers, and gene-by-smoking interactions are expected to affect COPD onset. We aimed to identify the common genetic variants interacting with pack-years of smoking on FEV(1)/FVC ratios in individuals with normal lung function. A genome-wide interaction study (GWIS) on FEV(1)/FVC was performed for individuals with FEV(1)/FVC ratio ≥ 70 in the Korea Associated Resource cohort data, and significant SNPs were validated using data from two other Korean cohorts. The GWIS revealed that rs10947231 and rs8192575 met genome-wide significant levels; For [Formula: see text] the likelihood ratio (LR) test was conducted, and its P values, P(LR), for rs10947231 and rs8192575 were 2.23 × 10(–12) and 1.18 × 10(–8), respectively. Interaction between rs8192575 and smoking is significantly replicated with two additional data (P(INT) = 0.0454, 0.0131). Expression quantitative trait loci, topologically associated domains, and PrediXcan analyses revealed that rs8192575 is significantly associated with AGER expression. SNPs on the 6p21 region are associated with FEV(1)/FVC, and the effect of smoking on FEV(1)/FVC differs among the associated genotypes. Nature Publishing Group UK 2020-08-04 /pmc/articles/PMC7403370/ /pubmed/32753590 http://dx.doi.org/10.1038/s41598-020-70092-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Park, Boram
An, Jaehoon
Kim, Wonji
Kang, Hae Yeon
Koh, Sang Baek
Oh, Bermseok
Jung, Keum Ji
Jee, Sun Ha
Kim, Woo Jin
Cho, Michael H.
Silverman, Edwin K.
Park, Taesung
Won, Sungho
Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study
title Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study
title_full Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study
title_fullStr Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study
title_full_unstemmed Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study
title_short Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study
title_sort effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403370/
https://www.ncbi.nlm.nih.gov/pubmed/32753590
http://dx.doi.org/10.1038/s41598-020-70092-0
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