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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Genetic influence on lung functions has been identified in previous studies; however, the relative longitudinal effects of genetic factors and their interactions with smoking on lung function remain unclear. Here, we identified the longitudinal effects of genetic variants on lung function by determining single nucleotide polymorphism (SNP) heritability and genetic correlations, and by analyzing interactions with smoking. Subject-specific means and annual change rates were calculated for eight spirometric measures obtained from 6622 Korean adults aged 40–69 years every two years for 14 years, and their heritabilities were estimated separately. Statistically significant (p < 0.05) heritability for the subject-specific means of all spirometric measures (8~32%) and change rates of forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC; 16%) and post-bronchodilator FEV1/FVC (17%) were detected. Significant genetic correlations of the change rate with the subject-specific mean were observed for FEV1/FVC (ρg = 0.64) and post-bronchodilator FEV1/FVC (ρg = 0.47). Furthermore, post-bronchodilator FEV1/FVC showed significant heritability of SNP-by-smoking interaction (hGXS2 = 0.4) for the annual change rate. The GWAS also detected genome-wide significant SNPs for FEV1 (rs4793538), FEV1/FVC (rs2704589, rs62201158, and rs9391733), and post-bronchodilator FEV1/FVC (rs2445936). We found statistically significant evidence of heritability role on the change in lung function, and this was shared with the effects on cross-sectional measurements. We also found some evidence of interaction with smoking for the change of lung function.

Details

Title
Heritability Analyses Uncover Shared Genetic Effects of Lung Function and Change over Time
Author
Li, Donghe 1 ; Kim, Woojin 2   VIAFID ORCID Logo  ; An, Jahoon 3 ; Kim, Soriul 4   VIAFID ORCID Logo  ; Lee, Seungku 4 ; Do, Ahra 5   VIAFID ORCID Logo  ; Kim, Wonji 6   VIAFID ORCID Logo  ; Lee, Sanghun 7   VIAFID ORCID Logo  ; Yoon, Dankyu 8 ; Lee, Kwangbae 9 ; Ha, Seounguk 9   VIAFID ORCID Logo  ; Silverman, Edwin K 6 ; Cho, Michael 6 ; Shin, Chol 10   VIAFID ORCID Logo  ; Won, Sungho 11   VIAFID ORCID Logo 

 Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 08826, Korea; [email protected] (D.L.); [email protected] (A.D.); Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA 02118, USA 
 Department of Internal Medicine and Environmental Health Center, School of Medicine, Kangwon National University, Chuncheon 24341, Korea; [email protected] 
 Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul 08826, Korea; [email protected] 
 Institute for Human Genomic Study, College of Medicine, Korea University, Seoul 136701, Korea; [email protected] (S.K.); [email protected] (S.L.) 
 Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 08826, Korea; [email protected] (D.L.); [email protected] (A.D.) 
 Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA; [email protected] (W.K.); [email protected] (E.K.S.); [email protected] (M.C.) 
 Department of Medical Consilience, Graduate School, Dankook University, Yongin 16890, Korea; [email protected] 
 Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju 28159, Korea; [email protected] 
 Korea Medical Institute, Seoul 03173, Korea; [email protected] (K.L.); [email protected] (S.H.) 
10  Institute for Human Genomic Study, College of Medicine, Korea University, Seoul 136701, Korea; [email protected] (S.K.); [email protected] (S.L.); Division of Pulmonary Sleep and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Korea 
11  Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 08826, Korea; [email protected] (D.L.); [email protected] (A.D.); Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul 08826, Korea; [email protected]; Institute of Health and Environment, Seoul National University, Seoul 08826, Korea; RexSoft Inc., Seoul 08826, Korea 
First page
1261
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
20734425
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2694003928
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.