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dc.contributor.authorZhang, Ruyang
dc.contributor.authorZhao, Yang
dc.contributor.authorChu, Minjie
dc.contributor.authorMehta, Amar Jayant
dc.contributor.authorWei, Yongyue
dc.contributor.authorLiu, Yao
dc.contributor.authorXun, Pengcheng
dc.contributor.authorBai, Jianling
dc.contributor.authorYu, Hao
dc.contributor.authorSu, Li
dc.contributor.authorZhang, Hongxi
dc.contributor.authorHu, Zhibin
dc.contributor.authorShen, Hongbing
dc.contributor.authorChen, Feng
dc.contributor.authorChristiani, David C.
dc.date.accessioned2013-05-07T14:37:28Z
dc.date.issued2013
dc.identifier.citationZhang, Ruyang, Yang Zhao, Minjie Chu, Amar Mehta, Yongyue Wei, Yao Liu, Pengcheng Xun, et al. 2013. A large scale gene-centric association study of lung function in newly-hired female cotton textile workers with endotoxin exposure. PLoS ONE 8(3): e59035.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10611678
dc.description.abstractBackground: 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.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0059035en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602449/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectComputational Biologyen_US
dc.subjectGenomicsen_US
dc.subjectGenome Analysis Toolsen_US
dc.subjectGenetic Screensen_US
dc.subjectGenome-Wide Association Studiesen_US
dc.subjectPopulation Geneticsen_US
dc.subjectGenetic Polymorphismen_US
dc.subjectGeneticsen_US
dc.subjectHuman Geneticsen_US
dc.subjectPopulation Biologyen_US
dc.subjectEpidemiologyen_US
dc.subjectGenetic Epidemiologyen_US
dc.subjectMedicineen_US
dc.subjectNon-Clinical Medicineen_US
dc.subjectEnvironmental Healthen_US
dc.subjectPublic Healthen_US
dc.subjectOccupational and Industrial Healthen_US
dc.subjectPulmonologyen_US
dc.subjectChronic Obstructive Pulmonary Diseasesen_US
dc.subjectEnvironmental and Occupational Lung Diseasesen_US
dc.subjectInterstitial Lung Diseasesen_US
dc.titleA Large Scale Gene-Centric Association Study of Lung Function in Newly-Hired Female Cotton Textile Workers with Endotoxin Exposureen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorChristiani, David C.
dc.date.available2013-05-07T14:37:28Z
dc.identifier.doi10.1371/journal.pone.0059035*
dash.authorsorderedfalse
dash.contributor.affiliatedWei, Yongyue
dash.contributor.affiliatedSu, Li
dash.contributor.affiliatedMehta, A
dash.contributor.affiliatedChristiani, David


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