A genome-wide association study of quantitative computed tomographic emphysema in Korean populations
Abstract Emphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema seve...
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Nature Portfolio
2021
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oai:doaj.org-article:22655ed4fce14543bd5efc7b206a09b32021-12-02T15:10:50ZA genome-wide association study of quantitative computed tomographic emphysema in Korean populations10.1038/s41598-021-95887-72045-2322https://doaj.org/article/22655ed4fce14543bd5efc7b206a09b32021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95887-7https://doaj.org/toc/2045-2322Abstract Emphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema severity and characterize the potential function of the associated loci in Korean population. We performed a genome-wide association study (GWAS) on quantitative emphysema in subjects with or without COPD from two Korean COPD cohorts. We investigated the functional consequences of the loci using epigenetic annotation and gene expression data. We also compared our GWAS results with an epigenome-wide association study and previous differential gene expression analysis. In total, 548 subjects (476 [86.9%] male) including 514 COPD patients were evaluated. We identified one genome-wide significant SNP (P < 5.0 × 10–8), rs117084279, near PIBF1. We identified an additional 57 SNPs (P < 5.0 × 10–6) associated with emphysema in all subjects, and 106 SNPs (P < 5.0 × 10–6) in COPD patients. Of these candidate SNPs, 2 (rs12459249, rs11667314) near CYP2A6 were expression quantitative trait loci in lung tissue and a SNP (rs11214944) near NNMT was an expression quantitative trait locus in whole blood. Of note, rs11214944 was in linkage disequilibrium with variants in enhancer histone marks in lung tissue. Several genes near additional SNPs were identified in our previous EWAS study with nominal level of significance. We identified a novel SNP associated with quantitative emphysema on CT. Including the novel SNP, several candidate SNPs in our study may provide clues to the genetic etiology of emphysema in Asian populations. Further research and validation of the loci will help determine the genetic factors for the development of emphysema.Sooim SinHye-Mi ChoiJiwon LimJeeyoung KimSo Hyeon BakSun Shim ChoiJinkyeong ParkJin Hwa LeeYeon-Mok OhMi Kyeong LeeBrian D. HobbsMichael H. ChoEdwin K. SilvermanWoo Jin KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Sooim Sin Hye-Mi Choi Jiwon Lim Jeeyoung Kim So Hyeon Bak Sun Shim Choi Jinkyeong Park Jin Hwa Lee Yeon-Mok Oh Mi Kyeong Lee Brian D. Hobbs Michael H. Cho Edwin K. Silverman Woo Jin Kim A genome-wide association study of quantitative computed tomographic emphysema in Korean populations |
| description |
Abstract Emphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema severity and characterize the potential function of the associated loci in Korean population. We performed a genome-wide association study (GWAS) on quantitative emphysema in subjects with or without COPD from two Korean COPD cohorts. We investigated the functional consequences of the loci using epigenetic annotation and gene expression data. We also compared our GWAS results with an epigenome-wide association study and previous differential gene expression analysis. In total, 548 subjects (476 [86.9%] male) including 514 COPD patients were evaluated. We identified one genome-wide significant SNP (P < 5.0 × 10–8), rs117084279, near PIBF1. We identified an additional 57 SNPs (P < 5.0 × 10–6) associated with emphysema in all subjects, and 106 SNPs (P < 5.0 × 10–6) in COPD patients. Of these candidate SNPs, 2 (rs12459249, rs11667314) near CYP2A6 were expression quantitative trait loci in lung tissue and a SNP (rs11214944) near NNMT was an expression quantitative trait locus in whole blood. Of note, rs11214944 was in linkage disequilibrium with variants in enhancer histone marks in lung tissue. Several genes near additional SNPs were identified in our previous EWAS study with nominal level of significance. We identified a novel SNP associated with quantitative emphysema on CT. Including the novel SNP, several candidate SNPs in our study may provide clues to the genetic etiology of emphysema in Asian populations. Further research and validation of the loci will help determine the genetic factors for the development of emphysema. |
| format |
article |
| author |
Sooim Sin Hye-Mi Choi Jiwon Lim Jeeyoung Kim So Hyeon Bak Sun Shim Choi Jinkyeong Park Jin Hwa Lee Yeon-Mok Oh Mi Kyeong Lee Brian D. Hobbs Michael H. Cho Edwin K. Silverman Woo Jin Kim |
| author_facet |
Sooim Sin Hye-Mi Choi Jiwon Lim Jeeyoung Kim So Hyeon Bak Sun Shim Choi Jinkyeong Park Jin Hwa Lee Yeon-Mok Oh Mi Kyeong Lee Brian D. Hobbs Michael H. Cho Edwin K. Silverman Woo Jin Kim |
| author_sort |
Sooim Sin |
| title |
A genome-wide association study of quantitative computed tomographic emphysema in Korean populations |
| title_short |
A genome-wide association study of quantitative computed tomographic emphysema in Korean populations |
| title_full |
A genome-wide association study of quantitative computed tomographic emphysema in Korean populations |
| title_fullStr |
A genome-wide association study of quantitative computed tomographic emphysema in Korean populations |
| title_full_unstemmed |
A genome-wide association study of quantitative computed tomographic emphysema in Korean populations |
| title_sort |
genome-wide association study of quantitative computed tomographic emphysema in korean populations |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/22655ed4fce14543bd5efc7b206a09b3 |
| work_keys_str_mv |
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| _version_ |
1718387678972477440 |