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

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 (FEV(1)) 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 FEV(1) 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 FEV(1) 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 FEV(1) decline in cotton textile workers.