Identification of sex-specific DNA methylation changes driven by specific chemicals in cord blood in a Faroese birth cohort

Yuet-Kin Leung, Bin Ouyang, Liang Niu, Changchun Xie, Jun Ying, Mario Medvedovic, Aimin Chen, Pal Weihe, Damaskini Valvi, Philippe Grandjean, Shuk-Mei Ho

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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. We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. 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 HumanMethylation450 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. 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. In this multiple-pollutant and genome-wide study, we identified key epigenetic toxicants. The significant enrichment of specific X-chromosome sites in males implies potential sex-specific epigenome responses to prenatal chemical exposures.

OriginalsprogEngelsk
TidsskriftEpigenetics
Vol/bind13
Udgave nummer3
Sider (fra-til)290-300
ISSN1559-2294
DOI
StatusUdgivet - 4. mar. 2018

Fingeraftryk

Dichlorodiphenyl Dichloroethylene
DNA Methylation
Fetal Blood
Hexachlorobenzene
Chlorinated Hydrocarbons
Nervous System Diseases
Epigenomics
Food
DNA
Health
Population
Neoplasms

Citer dette

Leung, Yuet-Kin ; Ouyang, Bin ; Niu, Liang ; Xie, Changchun ; Ying, Jun ; Medvedovic, Mario ; Chen, Aimin ; Weihe, Pal ; Valvi, Damaskini ; Grandjean, Philippe ; Ho, Shuk-Mei. / Identification of sex-specific DNA methylation changes driven by specific chemicals in cord blood in a Faroese birth cohort. I: Epigenetics. 2018 ; Bind 13, Nr. 3. s. 290-300.
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abstract = "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. We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. 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 HumanMethylation450 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. 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. In this multiple-pollutant and genome-wide study, we identified key epigenetic toxicants. The significant enrichment of specific X-chromosome sites in males implies potential sex-specific epigenome responses to prenatal chemical exposures.",
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Identification of sex-specific DNA methylation changes driven by specific chemicals in cord blood in a Faroese birth cohort. / Leung, Yuet-Kin; Ouyang, Bin; Niu, Liang; Xie, Changchun; Ying, Jun; Medvedovic, Mario; Chen, Aimin; Weihe, Pal; Valvi, Damaskini; Grandjean, Philippe; Ho, Shuk-Mei.

I: Epigenetics, Bind 13, Nr. 3, 04.03.2018, s. 290-300.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Identification of sex-specific DNA methylation changes driven by specific chemicals in cord blood in a Faroese birth cohort

AU - Leung, Yuet-Kin

AU - Ouyang, Bin

AU - Niu, Liang

AU - Xie, Changchun

AU - Ying, Jun

AU - Medvedovic, Mario

AU - Chen, Aimin

AU - Weihe, Pal

AU - Valvi, Damaskini

AU - Grandjean, Philippe

AU - Ho, Shuk-Mei

PY - 2018/3/4

Y1 - 2018/3/4

N2 - 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. We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. 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 HumanMethylation450 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. 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. In this multiple-pollutant and genome-wide study, we identified key epigenetic toxicants. The significant enrichment of specific X-chromosome sites in males implies potential sex-specific epigenome responses to prenatal chemical exposures.

AB - 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. We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. 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 HumanMethylation450 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. 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. In this multiple-pollutant and genome-wide study, we identified key epigenetic toxicants. The significant enrichment of specific X-chromosome sites in males implies potential sex-specific epigenome responses to prenatal chemical exposures.

KW - 450K

KW - BeadChips

KW - DDT

KW - HCB

KW - PCB105

KW - PFOS

KW - POPs

KW - X-chromosome

KW - cord blood

KW - epidemiology

KW - epigenetics

KW - gender difference

KW - hexachlorobenzene

KW - persistent organic pollutants

KW - polychlorinated biphenyls

U2 - 10.1080/15592294.2018.1445901

DO - 10.1080/15592294.2018.1445901

M3 - Journal article

VL - 13

SP - 290

EP - 300

JO - Epigenetics

JF - Epigenetics

SN - 1559-2294

IS - 3

ER -