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PLoS One. 2013;8(3):e59035. doi: 10.1371/journal.pone.0059035. Epub 2013 Mar 19.

A large scale gene-centric association study of lung function in newly-hired female cotton textile workers with endotoxin exposure.

Author information

1
Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.

Abstract

BACKGROUND:

Occupational exposure to endotoxin is associated with decrements in pulmonary function, but how much variation in this association is explained by genetic variants is not well understood.

OBJECTIVE:

We aimed to identify single nucleotide polymorphisms (SNPs) that are associated with the rate of forced expiratory volume in one second (FEV1) decline by a large scale genetic association study in newly-hired healthy young female cotton textile workers.

METHODS:

DNA samples were genotyped using the Illumina Human CVD BeadChip. Change rate in FEV1 was modeled as a function of each SNP genotype in linear regression model with covariate adjustment. We controlled the type 1 error in study-wide level by permutation method. The false discovery rate (FDR) and the family-wise error rate (FWER) were set to be 0.10 and 0.15 respectively.

RESULTS:

Two SNPs were found to be significant (P<6.29×10(-5)), including rs1910047 (P = 3.07×10(-5), FDR = 0.0778) and rs9469089 (P = 6.19×10(-5), FDR = 0.0967), as well as other eight suggestive (P<5×10(-4)) associated SNPs. Gene-gene and gene-environment interactions were also observed, such as rs1910047 and rs1049970 (P = 0.0418, FDR = 0.0895); rs9469089 and age (P = 0.0161, FDR = 0.0264). Genetic risk score analysis showed that the more risk loci the subjects carried, the larger the rate of FEV1 decline occurred (P trend = 3.01×10(-18)). However, the association was different among age subgroups (P = 7.11×10(-6)) and endotoxin subgroups (P = 1.08×10(-2)). Functional network analysis illustrates potential biological connections of all interacted genes.

CONCLUSIONS:

Genetic variants together with environmental factors interact to affect the rate of FEV1 decline in cotton textile workers.

PMID:
23527081
PMCID:
PMC3602449
DOI:
10.1371/journal.pone.0059035
[Indexed for MEDLINE]
Free PMC Article
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