Respiratory traits and coal workers’ pneumoconiosis: Mendelian randomisation and association analysis

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.