A Large Scale Gene-Centric Association Study of Lung Function in Newly-Hired Female Cotton Textile Workers with Endotoxin Exposure

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 (Ptrend = 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.