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.
- coal dust
- genetic susceptibility
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TW, WS, HW and YC contributed equally.
Correction notice This article has been corrected since it was published Online First. The author name Yuxin Cheng was previously spelt incorrectly as Yuxing Cheng.
Contributors TW, WS, HW and YC are joint first authors. Study design was led by TW, FM and CN. Data collection was carried out by WS, HW and YC. Statistical analyses were conducted by TW and YL. TW, WS, HW and YC drafted the manuscript. FM and CN revised the manuscript and approved the final version.
Funding This work was supported by the National Natural Science Foundation of China Nos. (81602813; 81874258).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval This study was approved by the institutional review board of Nanjing Medical University.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. The detailed information of SNPs derived from published GWAS would be available on request from the corresponding authors.