title: 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 (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.
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Ruyang
authors.initials: R
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Minjie
authors.initials: M
authors.lastname: Chu
authors.forename: Amar
authors.initials: A
authors.lastname: Mehta
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Wei
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Xun
authors.forename: Jianling
authors.initials: J
authors.lastname: Bai
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.forename: Hongxi
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000293:Adolescent; D000328:Adult; D002095:Byssinosis / Q000209:etiology*; D004731:Endotoxins; D004843:Epistasis, Genetic; D005260:Female; D005541:Forced Expiratory Volume; D053263:Gene Regulatory Networks; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009784:Occupational Diseases / Q000209:etiology*; D016273:Occupational Exposure; D020641:Polymorphism, Single Nucleotide; D012129:Respiratory Function Tests; D013784:Textiles; D055815:Young Adult
chemical_list: D004731:Endotoxins