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

Boram Park; Jaehoon An; Wonji Kim; Hae Yeon Kang; Sang Baek Koh; Bermseok Oh; Keum Ji Jung; Sun Ha Jee; Woo Jin Kim; Michael H. Cho; Edwin K. Silverman; Taesung Park; Sungho Won

doi:10.1038/s41598-020-70092-0

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

Boram Park, Jaehoon An, Wonji Kim, Hae Yeon Kang, Sang Baek Koh, Bermseok Oh, Keum Ji Jung, Sun Ha Jee, Woo Jin Kim, Michael H. Cho, Edwin K. Silverman, Taesung Park, Sungho Won

Preventive medicine

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

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 FEV₁/FVC ratios in individuals with normal lung function. A genome-wide interaction study (GWIS) on FEV₁/FVC was performed for individuals with FEV₁/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 H0:βSNP=βSNP∗pack-years=0vs H1:notH0, 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 FEV₁/FVC, and the effect of smoking on FEV₁/FVC differs among the associated genotypes.

Original language	English
Article number	13075
Journal	Scientific reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-70092-0
Publication status	Published - 2020 Dec 1

Bibliographical note

Funding Information:
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C2165), and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A1A09919610).

Publisher Copyright:
© 2020, The Author(s).

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10.1038/s41598-020-70092-0

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@article{74361614b2894a658370120cb261f49e,

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

abstract = "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 FEV1/FVC ratios in individuals with normal lung function. A genome-wide interaction study (GWIS) on FEV1/FVC was performed for individuals with FEV1/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 H0:βSNP=βSNP∗pack-years=0vs H1:notH0, the likelihood ratio (LR) test was conducted, and its P values, PLR, 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 (PINT = 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 FEV1/FVC, and the effect of smoking on FEV1/FVC differs among the associated genotypes.",

author = "Boram Park and Jaehoon An and Wonji Kim and Kang, {Hae Yeon} and Koh, {Sang Baek} and Bermseok Oh and Jung, {Keum Ji} and Jee, {Sun Ha} and Kim, {Woo Jin} and Cho, {Michael H.} and Silverman, {Edwin K.} and Taesung Park and Sungho Won",

note = "Funding Information: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C2165), and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A1A09919610). Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

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doi = "10.1038/s41598-020-70092-0",

language = "English",

volume = "10",

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T1 - Effect of 6p21 region on lung function is modified by smoking

T2 - a genome-wide interaction study

AU - Park, Boram

AU - An, Jaehoon

AU - Kim, Wonji

AU - Kang, Hae Yeon

AU - Koh, Sang Baek

AU - Oh, Bermseok

AU - Jung, Keum Ji

AU - Jee, Sun Ha

AU - Kim, Woo Jin

AU - Cho, Michael H.

AU - Silverman, Edwin K.

AU - Park, Taesung

AU - Won, Sungho

N1 - Funding Information: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C2165), and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A1A09919610). Publisher Copyright: © 2020, The Author(s).

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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 FEV1/FVC ratios in individuals with normal lung function. A genome-wide interaction study (GWIS) on FEV1/FVC was performed for individuals with FEV1/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 H0:βSNP=βSNP∗pack-years=0vs H1:notH0, the likelihood ratio (LR) test was conducted, and its P values, PLR, 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 (PINT = 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 FEV1/FVC, and the effect of smoking on FEV1/FVC differs among the associated genotypes.

AB - 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 FEV1/FVC ratios in individuals with normal lung function. A genome-wide interaction study (GWIS) on FEV1/FVC was performed for individuals with FEV1/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 H0:βSNP=βSNP∗pack-years=0vs H1:notH0, the likelihood ratio (LR) test was conducted, and its P values, PLR, 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 (PINT = 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 FEV1/FVC, and the effect of smoking on FEV1/FVC differs among the associated genotypes.

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DO - 10.1038/s41598-020-70092-0

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SN - 2045-2322

VL - 10

JO - Scientific Reports

JF - Scientific Reports

IS - 1

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ER -

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

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