Respiratory traits and coal workers' pneumoconiosis: Mendelian randomisation and association analysis.

Autor:	Wang T; Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China chninjmu@126.com wangti08@163.com., Sun W; Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu, China., Wu H; Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China., Cheng Y; Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China., Li Y; Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu, China., Meng F; Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China., Ni C; Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu, China chninjmu@126.com wangti08@163.com.
Jazyk:	angličtina
Zdroj:	Occupational and environmental medicine [Occup Environ Med] 2021 Feb; Vol. 78 (2), pp. 137-141. Date of Electronic Publication: 2020 Oct 23.
DOI:	10.1136/oemed-2020-106610
Abstrakt:	Objectives: Susceptibility loci of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease were also significantly associated with the predisposition of coal worker's pneumoconiosis (CWP) in recent studies. However, only a few genes and loci were targeted in previous studies. Methods: To systematically evaluate the genetic associations between CWP and other respiratory traits, we reviewed the reported genome-wide association study loci of five respiratory traits and then conducted a Mendelian randomisation study and a two-stage genetic association study. Results: Interestingly, we found that for each SD unit, higher lung function was associated with a 66% lower risk of CWP (OR=0.34, 95% CI: 0.15 to 0.77, p=0.010) using conventional Mendelian randomisation analysis (inverse variance weighted method). Moreover, we found susceptibility loci of interstitial lung disease (rs2609255, OR=1.29, p=1.61×10 -4 ) and lung function (rs4651005, OR=1.39, p=1.62×10 -3 ; rs985256, OR=0.73, p=8.24×10 -4 and rs6539952, OR=1.28, p=4.32×10 -4 ) were also significantly associated with the risk of CWP. Functional annotation showed these variants were significantly associated with the expression of FAM13A (rs2609255, p=7.4 ×10 -4 ), ANGPTL1 (rs4651005, p=5.4 ×10 -7 ), SPATS2L (rs985256, p=1.1 ×10 -5 ) and RP11-463O9.9 (rs6539952, p=7.1 ×10 -6 ) in normal lung tissues, which were related to autophagy pathway simultaneously according to enrichment analysis. Conclusions: These results provided a deeper understanding of the genetic predisposition basis of CWP. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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