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- Title
Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study.
- Authors
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
- 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 H 0 : β SNP = β S N P ∗ p a c k - y e a r s = 0 vs H 1 : n o t H 0 , 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.
- Subjects
LUNG physiology; OBSTRUCTIVE lung diseases; PHYSIOLOGICAL effects of tobacco; LUNG diseases; GENOTYPES
- Publication
Scientific Reports, 2020, Vol 10, Issue 1, pN.PAG
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-020-70092-0