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

Rui Zhao; Xiaobo Tao; Wendi Zhang; Siqi Li; Shenxuan Zhou; Anhui Ning; Zhenyu Li; Minjie Chu; Wei Wang; Junhong Jiang

doi:10.1016/j.ecoenv.2025.117679

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

Ecotoxicol Environ Saf. 2025 Jan 9:289:117679. doi: 10.1016/j.ecoenv.2025.117679. Online ahead of print.

Authors

Rui Zhao¹, Xiaobo Tao², Wendi Zhang², Siqi Li², Shenxuan Zhou², Anhui Ning², Zhenyu Li², Minjie Chu³, Wei Wang⁴, Junhong Jiang⁵

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; Department of Respiratory, Wuxi Eighth People's Hospital, Wuxi 214000, China.
² Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu, China.
³ Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu, China. Electronic address: [email protected].
⁴ Department of Occupational Health, Center for Disease Control and Prevention of Wuxi, Wuxi, China. Electronic address: [email protected].
⁵ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; Department of Pulmonary and Critical Care Medicine, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215000, China. Electronic address: [email protected].

PMID: 39793288
DOI: 10.1016/j.ecoenv.2025.117679

Abstract

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.

Keywords: MAD1L1; SERTAD2; SNPs; Silicosis; Susceptibility.