Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu, China.
Occup Environ Med. 2021 Feb;78(2):137-141. doi: 10.1136/oemed-2020-106610. Epub 2020 Oct 23.
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.
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.
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) and lung function (rs4651005, OR=1.39, p=1.62×10; rs985256, OR=0.73, p=8.24×10 and rs6539952, OR=1.28, p=4.32×10) were also significantly associated with the risk of CWP. Functional annotation showed these variants were significantly associated with the expression of (rs2609255, p=7.4 ×10), (rs4651005, p=5.4 ×10), (rs985256, p=1.1 ×10) and (rs6539952, p=7.1 ×10) in normal lung tissues, which were related to autophagy pathway simultaneously according to enrichment analysis.
These results provided a deeper understanding of the genetic predisposition basis of CWP.
最近的研究表明，特发性肺纤维化和慢性阻塞性肺疾病的易感基因也与煤工尘肺（CWP）的易感性显著相关。然而，之前的研究只针对少数几个基因和位点。
为了系统地评估 CWP 与其他呼吸特征的遗传相关性，我们回顾了报道的五个呼吸特征的全基因组关联研究位点，然后进行了孟德尔随机化研究和两阶段遗传关联研究。
有趣的是，我们发现使用传统的孟德尔随机化分析（逆方差加权法），每个标准差单位的肺功能越高，CWP 的风险降低 66%（OR=0.34，95%CI：0.15 至 0.77，p=0.010）。此外，我们还发现间质性肺病的易感基因(rs2609255，OR=1.29，p=1.61×10)和肺功能(rs4651005，OR=1.39，p=1.62×10；rs985256，OR=0.73，p=8.24×10 和 rs6539952，OR=1.28，p=4.32×10)与 CWP 的风险也显著相关。功能注释表明，这些变异与正常肺组织中 （rs2609255，p=7.4 ×10）、 （rs4651005，p=5.4 ×10）、 （rs985256，p=1.1 ×10）和 （rs6539952，p=7.1 ×10）的表达显著相关，根据富集分析，这些变异与自噬途径同时相关。
这些结果提供了对 CWP 遗传易感性基础的更深入理解。
