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CHDWB human plasma exposomics analysis - 1

ABSTRACT: We analyzed 80 archival samples from individuals (57 females, 23 males; aged 41 to 68 y) without known disease or occupational or environmental exposures of concern as a pilot to test the utility of XLE in large-scale human biomonitoring studies. Using a requirement for at least 3 co-eluting accurate mass m/z features ( 5 ppm) within 30 s of database retention time, we identified 49 chemicals belonging to various environmental chemical classes. An unsupervised 2-way hierarchical cluster analysis (HCA) of log transformed intensity showed clustering according to chemical class. In particular, persistent chemicals were highly correlated with each other (all raw P < 0.001), including p,p’-DDE, PCBs 153, 180, 138, 118 and 74, PBDE-47, hexachlorobenzene (HCB) and trans-nonachlor. Results showed a general increase of chemical levels with increasing age quartiles (Q3 and Q4 : 53 to 68 versus Q1 and Q2: 41 to 52) using unsupervised clustering, a trend particularly evident for the cluster of p,p’-DDE, PCBs 153, 180, 138, 118 and 74, PBDE-47, HCB and trans-nonachlor. Examination of data according to body mass index (BMI) showed that individuals with BMI ≥ 40 had lower levels of environmental chemicals, which may be attributed to high lipophilicity and propensity to distribute in adipose tissue versus plasma. Quantification with reference standardization showed that use of two SRM samples with differing environmental chemical concentrations can overcome variable batch effects in quantification for large-scale studies. Examples of the most frequently detected chemicals shows that overall distributions were positively skewed by a small subset of individuals with high concentrations.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

SUBMITTER: Xin Hu

PROVIDER: ST001801 | MetabolomicsWorkbench | Thu May 06 00:00:00 BST 2021

REPOSITORIES: MetabolomicsWorkbench

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Project description:Genome wide DNA methylation profiling of cord blood in Faroe Island cohort. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,000 CpGs in cord blood samples. Background: Faroe islanders consume marine foods contaminated with methylmercury (MeHg), polychlorinated biphenyls (PCBs), and other toxicants associated with chronic disease risks. Differential DNA methylation at specific CpG sites in cord blood may serve as a surrogate biomarker of health impacts from chemical exposures. Objective: We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. Method: We studied 72 participants of a Faroese birth cohort recruited between 1986 and 1987 and followed until adulthood. The cord blood DNA methylome was profiled using Infinium Methylation 450K BeadChips. We determined the associations of CpG site changes with concentrations of MeHg, major PCBs, other organochlorine compounds, (hexachlorobenzene [HCB], p,p’-dichlorodiphenyldichloroethylene [p,p’-DDE] and p,p’-dichlorodiphenyltrichloroethane) and perfluoroalkyl substances. Results: In a combined sex analysis, among the 16 chemicals studied, PCB congener 105 (CB-105) exposure was associated with the majority of differentially methylated CpG sites (214 out of a total of 250). In female-only-analysis, only 73 CB-105 associated CpG sites were detected, 44 of which were mapped to genes in the ELAV1-associated cancer network. In males-only, methylation changes were seen for perfluorooctane sulfonate, HCB, and p,p’-DDE in 10,598; 1,238; and 1,473 CpG sites, respectively, 15% of which were enriched in cytobands of the X chromosome associated with neurological disorders. Conclusion: In this multiple-pollutant and genome-wide study, we identified key epigenetic toxicants. The significant enrichment of specific X-chromosome sites in males implies potentially sex-specific epigenome responses to prenatal chemical exposures.

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CHDWB human plasma exposomics analysis - 1

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