A large scale gene-centric association study of lung function in newly-hired female cotton textile workers with endotoxin exposure.
A large scale gene-centric association study of lung function in newly-hired female cotton textile workers with endotoxin exposure.
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内毒素暴露新入职女棉纺织工人肺功能的大规模以基因为中心的关联研究
DOI：
10.1371/journal.pone.0059035
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Christiani DC
中科院分区：
文献类型：
--
作者：
Zhang R;Zhao Y;Chu M;Mehta A;Wei Y;Liu Y;Xun P;Bai J;Yu H;Su L;Zhang H;Hu Z;Shen H;Chen F;Christiani DC
职业性接触内毒素与肺功能下降相关，但基因变异能在多大程度上解释这种关联，目前尚不清楚。
我们旨在通过对新入职的健康年轻女性棉纺织工人开展大规模基因关联研究，找出与一秒用力呼气量（FEV1）下降速率相关的单核苷酸多态性（SNP）。
使用Illumina人类心血管疾病基因芯片对DNA样本进行基因分型。在协变量调整后的线性回归模型中，将FEV1变化率作为每个SNP基因型的函数进行建模。我们通过置换法在全研究层面控制一类错误。错误发现率（FDR）和族系错误率（FWER）分别设定为0.10和0.15。
发现两个SNP具有显著性（P < 6.29×10⁻⁵），包括rs1910047（P = 3.07×10⁻⁵，FDR = 0.0778）和rs9469089（P = 6.19×10⁻⁵，FDR = 0.0967），以及另外八个提示性（P < 5×10⁻⁴）相关的SNP。还观察到了基因 - 基因以及基因 - 环境相互作用，例如rs1910047与rs1049970（P = 0.0418，FDR = 0.0895）；rs9469089与年龄（P = 0.0161，FDR = 0.0264）。遗传风险评分分析表明，受试者携带的风险位点越多，FEV1下降速率越大（P趋势 = 3.01×10⁻¹⁸）。然而，这种关联在不同年龄亚组（P = 7.11×10⁻⁶）和内毒素亚组（P = 1.08×10⁻²）中存在差异。功能网络分析展示了所有相互作用基因的潜在生物学联系。
基因变异与环境因素相互作用，影响棉纺织工人FEV1的下降速率。
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.
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DOI：
10.1164/rccm.200811-1757st
发表时间：
2010-09-01
影响因子：
24.7
作者：
Eisner, Mark D.;Anthonisen, Nicholas;Balmes, John R.
通讯作者：
Balmes, John R.
影响因子：
14.9
作者：
Heinemeyer, T;Wingender, E;Kolchanov, NA
通讯作者：
Kolchanov, NA
影响因子：
30.8
作者：
Barton A;Thomson W;Ke X;Eyre S;Hinks A;Bowes J;Plant D;Gibbons LJ;Wellcome Trust Case Control Consortium;YEAR Consortium;BIRAC Consortium;Wilson AG;Bax DE;Morgan AW;Emery P;Steer S;Hocking L;Reid DM;Wordsworth P;Harrison P;Worthington J
通讯作者：
Worthington J
影响因子：
3.7
作者：
Dai J;Gu J;Lu C;Lin J;Stewart D;Chang D;Roth JA;Wu X
通讯作者：
Wu X
影响因子：
10.4
作者：
Imboden M;Schwartz J;Schindler C;Curjuric I;Berger W;Liu SL;Russi EW;Ackermann-Liebrich U;Rochat T;Probst-Hensch NM;SAPALDIA Team
通讯作者：
SAPALDIA Team