title: Genetic variants, PM2.5exposure level and global DNA methylation level: A multi-center population-based study in Chinese.
abstract: Global DNA methylation levels can be determined by environmental and genetic factors. There are emerging evidences that methylation status can be modified as exposed to environmental factors such as PM2.5, but the genetic determinants are still largely unknown. To explore whether genetic variants contribute to global DNA methylation levels with consideration of environmental exposures, we systematically evaluated the association between genetic variants and global DNA methylation levels in 301 subjects from three cities in southern, central and northern China with different PM2.5exposure levels (Zhuhai, Wuhan and Tianjin, respectively). Personal 24-h PM2.5exposure levels and global DNA methylation levels for each subject were evaluated. Using Illumina Human Exome BeadChip, 241,305 SNVs was genotyped and assessed for their association with global DNA methylation levels. We found that after adjusting for age, gender, PM2.5exposure level, pack-years of smoking and BMI, 14 SNVs were consistently associated with global DNA methylation levels with pooled P≤1.00×10-4after meta-analysis of three cohorts, in which 8 SNVs together with age were independent factors modifying global DNA methylation levels. Joint analysis of these identified SNVs showed a significant allele-dosage association between the number of variants and global DNA methylation levels (P=1.82×10-23). In particular, we detected a significant multiplicative interaction between rs4344916 on chromosome 2p22.3 and PM2.5exposure on global DNA methylation level (P=0.0095). Our findings indicate that genetic variants alone or in combination with PM2.5play an important role in modifying individual global DNA methylation levels.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Chronic Non-Communicable Disease Control, Wuxi Center for Disease Control and Prevention, Wuxi, Jiangsu, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China; Nanjing Maternal and Child Health Institute, Nanjing Maternal and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Kaipeng
authors.initials: K
authors.lastname: Xie
authors.affiliation: Ministry of Education Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Ministry of Education Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Liguo
authors.initials: L
authors.lastname: Geng
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jiangbo
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Ministry of Education Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: hbshen@njmu.edu.cn.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000368:Aged; D000393:Air Pollutants / Q000633:toxicity; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002681:China; D015331:Cohort Studies; D019175:DNA Methylation; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D052638:Particulate Matter / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter
keywords: Genetic variants; Global DNA methylation; PM(2.5)