Novel functional eQTL-SNPs associated with susceptibility to occupational pulmonary fibrosis: A multi-stage study.

Aim: Identifying the common functional single-nucleotide polymorphisms (SNPs) that can both affect the susceptibility to idiopathic pulmonary fibrosis (IPF) and silicosis.

Methods: We first integrated the genome-wide association studies (GWASs) of IPF and silicosis to obtain the shared SNPs. Following this, functional expression quantitative trait locus (eQTL)-SNPs were identified by the GTEx database. This was followed by the validation of the correlation between these eQTL-SNPs and silicosis susceptibility through an additional case-control study including 194 silicosis cases and 235 healthy controls.

Results: A total of 10 eQTL-SNPs that may affect silicosis susceptibility (P < 0.05) were obtained after the integration of the GWASs of IPF and silicosis, and a series of rigorous selection principles. Subsequently, the results of integrating the validation stage and the screening stage indicated that the variant T allele of rs1620530 located in the MAD1L1 (additive model: OR= 1.56, 95 % CI = 1.21-2.01, P = 0.001) and the variant G allele of rs2070063 located in the SERTAD2 (additive model: OR= 1.60, 95 % CI = 1.24-2.06, P < 0.001) were associated with increased silicosis susceptibility. The joint analysis indicated the risk of developing silicosis was higher in individuals who carried more unfavorable alleles of rs1620530 and rs2070063.

Conclusions: The rs1620530 and rs2070063 may affect the silicosis susceptibility by regulating the expression of the MAD1L1 and SERTAD2, respectively. Further biological experiments are warranted to elucidate the underlying biological mechanisms between these two SNPs and the increased susceptibility to silicosis.