title: Performance of genetic risk factors in prediction of trichloroethylene induced hypersensitivity syndrome.
abstract: Trichloroethylene induced hypersensitivity syndrome is dose-independent and potentially life threatening disease, which has become one of the serious occupational health issues and requires intensive treatment. To discover the genetic risk factors and evaluate the performance of risk prediction model for the disease, we conducted genomewide association study and replication study with total of 174 cases and 1761 trichloroethylene-tolerant controls. Fifty seven SNPs that exceeded the threshold for genome-wide significance (P < 5 × 10(-8)) were screened to relate with the disease, among which two independent SNPs were identified, that is rs2857281 at MICA (odds ratio, 11.92; P meta = 1.33 × 10(-37)) and rs2523557 between HLA-B and MICA (odds ratio, 7.33; P meta = 8.79 × 10(-35)). The genetic risk score with these two SNPs explains at least 20.9% of the disease variance and up to 32.5-fold variation in inter-individual risk. Combining of two SNPs as predictors for the disease would have accuracy of 80.73%, the area under receiver operator characteristic curves (AUC) scores was 0.82 with sensitivity of 74% and specificity of 85%, which was considered to have excellent discrimination for the disease, and could be considered for translational application for screening employees before exposure.
authors.affiliation: Key laboratory of Chemical Safety and Health, Chinese Centre for Disease Control and Prevention. National Institute for Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, 100050, China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Dai
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, China.
authors.forename: Hanlin
authors.initials: H
authors.lastname: Huang
authors.affiliation: Hospital for Occupational Diseases Control of Shenzhen, Shenzhen, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Key laboratory of Chemical Safety and Health, Chinese Centre for Disease Control and Prevention. National Institute for Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, 100050, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Niu
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen, China.
authors.forename: Mingrong
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key laboratory of Chemical Safety and Health, Chinese Centre for Disease Control and Prevention. National Institute for Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, 100050, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Bin
authors.affiliation: Center for Disease Control and Prevention of Yunnan province, Kunming, Yunnan, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Shandong Academy of Occupational Health and Occupational Medicine, Jinan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Jia
authors.affiliation: Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Hospital for Occupational Diseases Control of Shenzhen, Shenzhen, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yi
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen, China.
authors.forename: Qijun
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Institute of chemicals safety, Chinese academy of inspection and quarantine, Beijing, China.
authors.forename: Haishan
authors.initials: H
authors.lastname: Li
authors.affiliation: Health Supervision Institutionof Dongcheng Health Bureau, Beijing, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Food And Drug Administration Of Beijing Fengtai District, Beijing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zang
authors.affiliation: Weifang Medical University, Weifang, Shandong, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Zhai
authors.affiliation: Key laboratory of Chemical Safety and Health, Chinese Centre for Disease Control and Prevention. National Institute for Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, 100050, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Duan
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shen
authors.affiliation: Hospital for Occupational Diseases Control of Shenzhen, Shenzhen, China.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: He
authors.affiliation: Key laboratory of Chemical Safety and Health, Chinese Centre for Disease Control and Prevention. National Institute for Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, 100050, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Meng
authors.affiliation: Hospital for Occupational Diseases Control of Shenzhen, Shenzhen, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sha
authors.affiliation: Key laboratory of Chemical Safety and Health, Chinese Centre for Disease Control and Prevention. National Institute for Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, 100050, China.
authors.forename: Meili
authors.initials: M
authors.lastname: Shen
authors.affiliation: Key laboratory of Chemical Safety and Health, Chinese Centre for Disease Control and Prevention. National Institute for Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, 100050, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ye
authors.affiliation: Key laboratory of Chemical Safety and Health, Chinese Centre for Disease Control and Prevention. National Institute for Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, 100050, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Jia
authors.affiliation: Hospital for Occupational Diseases Control of Shenzhen, Shenzhen, China.
authors.forename: Yingping
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Hospital for Occupational Diseases Control of Shenzhen, Shenzhen, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Huang
authors.affiliation: Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Wu
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Shi
authors.affiliation: Hospital for Occupational Diseases Control of Shenzhen, Shenzhen, China.
authors.forename: Xianqing
authors.initials: X
authors.lastname: Huang
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen, China.
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen, China.
authors.forename: Longhai
authors.initials: L
authors.lastname: Luo
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen, China.
authors.forename: Sai
authors.initials: S
authors.lastname: Li
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen, China.
authors.forename: Jinyang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, China.
authors.forename: Laiyu
authors.initials: L
authors.lastname: Li
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key laboratory of Chemical Safety and Health, Chinese Centre for Disease Control and Prevention. National Institute for Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, 100050, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D016022:Case-Control Studies; D063926:Drug Hypersensitivity Syndrome / Q000209:etiology*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006649:Histocompatibility Antigens / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D014241:Trichloroethylene / Q000009:adverse effects*
chemical_list: D018685:Anesthetics, Inhalation; D006649:Histocompatibility Antigens; D014241:Trichloroethylene