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Updated: Jun 19, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
The single nucleotide polymorphism rs155787 on the autophagy gene of SQSTM1 is associated with silicosis
Lijing Jiang1, Fan Wang2, Mingwei Huai3
1The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi 214023, China; Helie Subdistrict Community Health Service Center, Wuxi 214072, China.
Objective:
To investigate the association between single nucleotide polymorphisms (SNPs) in autophagy-related genes (ATGs) and susceptibility to silicosis.
Methods:
Used silicosis genome-wide association study (GWAS) data and multiple publicly available databases to identify autophagy-associated positive expression quantitative trait locus (eQTL)-SNPs. Candidate positive SNPs were subsequently validated for their association with silicosis susceptibility in an independent population. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to explore the expression of target genes. Finally, gene enrichment analysis was performed to preliminary explore the biological functions and potential pathways associated with the identified susceptibility genes.
Results:
A total of 15 SNPs in 10 ATGs were finally obtained after screening. Validation phase results indicated a significant association between the mutant G allele of rs155787 on the Sequestosome 1 (SQSTM1) and an increased risk of silicosis (additive model: odds ratio (OR)= 1.55, 95 % confidence interval (95 % CI): 1.05-2.28, P = 0.027). Combining GWAS and validation phase data, the mutant G allele was correlated with heightened silicosis susceptibility (additive model: OR=1.70, 95 % CI: 1.22-2.36, P = 0.002). The eQTL results indicated that significantly higher SQSTM1 expression in AG and GG genotypes than in AA genotypes (P < 0.05). Bioinformatics analysis revealed that SQSTM1 may bind to a range of autophagy proteins and immunoproteins to activate the biological process of macroautophagy, which influences the development of silicosis.
Conclusion:
The rs155787 locus on the SQSTM1 may be associated with silicosis susceptibility, and the mutant G allele may serve as a potential risk factor. Furthermore, the A>G variation at this locus was observed to upregulate SQSTM1 gene expression. Additional large-scale studies are necessary to further validate our findings.
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