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

• Published in: PloS one Vol. 8; no. 3; p. e59035
• Main Authors: Zhang, Ruyang, Zhao, Yang, Chu, Minjie, Mehta, Amar, Wei, Yongyue, Liu, Yao, Xun, Pengcheng, Bai, Jianling, Yu, Hao, Su, Li, Zhang, Hongxi, Hu, Zhibin, Shen, Hongbing, Chen, Feng, Christiani, David C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.03.2013; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Biology; Biomarkers; Byssinosis - etiology; Cancer; Cell cycle; Chronic obstructive pulmonary disease; Cotton; Deoxyribonucleic acid; Disease; Disease prevention; DNA; Education; Endotoxins; Environmental factors; Environmental health; Epidemiology; Epistasis, Genetic; Error analysis; Female; Females; Forced Expiratory Volume; Gene Regulatory Networks; Gene-Environment Interaction; Genes; Genetic analysis; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genomes; Genotypes; Hospitals; Humans; Laboratories; Lungs; Medicine; Middle Aged; Network analysis; Occupational Diseases - etiology; Occupational Exposure; Occupational health; Permutations; Polymorphism, Single Nucleotide; Proteins; Public health; Pulmonary functions; Regression analysis; Regression models; Respiratory function; Respiratory Function Tests; Rheumatoid arthritis; Risk analysis; Sampling methods; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Subgroups; Textile workers; Textiles; Toxicology; Tumor necrosis factor-TNF; Young Adult; Indiana; United States > US; Switzerland; China; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0059035

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