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.