Abstract
BackgroundOccupational 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.ObjectiveWe 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.MethodsDNA 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.ResultsTwo 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.ConclusionsGenetic variants together with environmental factors interact to affect the rate of FEV1 decline in cotton textile workers.
Highlights
According to an official statement from the American Thoracic Society (ATS) [1], cigarette smoking is not the sole meaningful cause of chronic obstructive pulmonary disease (COPD)
Genetic variants together with environmental factors interact to affect the rate of FEV1 decline in cotton textile workers
We aimed to explore the association between the rate of FEV1 decline and genetic heterogeneity in previously unexposed newly-hired young healthy female cotton textile workers entering endotoxin-exposed work areas in yarn preparation based on large scale genomic data
Summary
According to an official statement from the American Thoracic Society (ATS) [1], cigarette smoking is not the sole meaningful cause of chronic obstructive pulmonary disease (COPD). There is strong evidence suggesting a causal relationship between COPD and occupational exposures (e.g. endotoxin [2]) or genetic syndromes (e.g. a1-antitrypsin deficiency [3]). Exposure to cotton dust leads to chronic respiratory disease and excessive loss of pulmonary function [5,6,7]. 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
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