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

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2 Citations (Scopus)


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.

Original languageEnglish
Article number13075
JournalScientific reports
Issue number1
Publication statusPublished - 2020 Dec 1

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© 2020, The Author(s).

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