Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life
Abstract Background In utero arsenic exposure may alter fetal developmental programming by altering DNA methylation, which may result in a higher risk of disease in later life. We evaluated the association between in utero arsenic exposure and DNA methylation (DNAm) in cord blood and its influence i...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-05-01
|
| Series: | Environmental Health |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12940-017-0262-0 |
| _version_ | 1818341263271788544 |
|---|---|
| author | Akhilesh Kaushal Hongmei Zhang Wilfried J. J. Karmaus Todd M. Everson Carmen J. Marsit Margaret R. Karagas Shih-Fen Tsai Hui-Ju Wen Shu-Li Wang |
| author_facet | Akhilesh Kaushal Hongmei Zhang Wilfried J. J. Karmaus Todd M. Everson Carmen J. Marsit Margaret R. Karagas Shih-Fen Tsai Hui-Ju Wen Shu-Li Wang |
| author_sort | Akhilesh Kaushal |
| collection | DOAJ |
| description | Abstract Background In utero arsenic exposure may alter fetal developmental programming by altering DNA methylation, which may result in a higher risk of disease in later life. We evaluated the association between in utero arsenic exposure and DNA methylation (DNAm) in cord blood and its influence in later life. Methods Genome-wide DNA methylation in cord blood from 64 subjects in the Taiwanese maternal infant and birth cohort was analyzed. Robust regressions were applied to assess the association of DNA methylation with in utero arsenic exposure. Multiple testing was adjusted by controlling false discovery rate (FDR) of 0.05. The DAVID bioinformatics tool was implemented for functional annotation analyses on the detected CpGs. The identified CpGs were further tested in an independent cohort. For the CpGs replicated in the independent cohort, linear mixed models were applied to assess the association of DNA methylation with low-density lipoprotein (LDL) at different ages (2, 5, 8, 11 and 14 years). Results In total, 579 out of 385,183 CpGs were identified after adjusting for multiple testing (FDR = 0.05), of which ~60% were positively associated with arsenic exposure. Functional annotation analysis on these CpGs detected 17 KEGG pathways (FDR = 0.05) including pathways for cardiovascular diseases (CVD) and diabetes mellitus. In the independent cohort, about 46% (252 out of 553 CpGs) of the identified CpGs showed associations consistent with those in the study cohort. In total, 11 CpGs replicated in the independent cohort were in the pathways related to CVD and diabetes mellitus. Via longitudinal analyses, we found at 5 out of the 11 CpGs methylation was associated with LDL over time and interactions between DNA methylation and time were observed at 4 of the 5 CpGs, cg25189764 (coeff = 0.157, p-value = 0.047), cg04986899 (coeff. For interaction [coeff.int] = 0.030, p-value = 0.024), cg04903360 (coeff.int = 0.026, p-value = 0.032), cg08198265 (coeff.int = −0.063, p-value = 0.0021), cg10473311 (coeff.int = −0.021, p-value = 0.027). Conclusion In utero arsenic exposure was associated with cord blood DNA methylation at various CpGs. The identified CpGs may help determine pathological epigenetic mechanisms linked to in utero arsenic exposure. Five CpGs (cg25189764, cg04986899, cg04903360, cg08198265 and cg10473311) may serve as epigenetic markers for changes in LDL later in life. |
| first_indexed | 2024-12-13T15:56:01Z |
| format | Article |
| id | doaj.art-abe5c6719fb14859b0134ee501ca41b4 |
| institution | Directory Open Access Journal |
| issn | 1476-069X |
| language | English |
| last_indexed | 2024-12-13T15:56:01Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Environmental Health |
| spelling | doaj.art-abe5c6719fb14859b0134ee501ca41b42022-12-21T23:39:19ZengBMCEnvironmental Health1476-069X2017-05-0116111110.1186/s12940-017-0262-0Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later lifeAkhilesh Kaushal0Hongmei Zhang1Wilfried J. J. Karmaus2Todd M. Everson3Carmen J. Marsit4Margaret R. Karagas5Shih-Fen Tsai6Hui-Ju Wen7Shu-Li Wang8Division of Epidemiology, Biostatistics, and Environmental Health, University of MemphisDivision of Epidemiology, Biostatistics, and Environmental Health, University of MemphisDivision of Epidemiology, Biostatistics, and Environmental Health, University of MemphisDepartment of Environmental Health, Rollins School of Public Health, Emory UniversityDepartment of Environmental Health, Rollins School of Public Health, Emory UniversityDepartment of Epidemiology, Geisel School of Medicine at Dartmouth CollegeNational Institute of Environmental Health Sciences, National Health Research InstitutesNational Institute of Environmental Health Sciences, National Health Research InstitutesNational Institute of Environmental Health Sciences, National Health Research InstitutesAbstract Background In utero arsenic exposure may alter fetal developmental programming by altering DNA methylation, which may result in a higher risk of disease in later life. We evaluated the association between in utero arsenic exposure and DNA methylation (DNAm) in cord blood and its influence in later life. Methods Genome-wide DNA methylation in cord blood from 64 subjects in the Taiwanese maternal infant and birth cohort was analyzed. Robust regressions were applied to assess the association of DNA methylation with in utero arsenic exposure. Multiple testing was adjusted by controlling false discovery rate (FDR) of 0.05. The DAVID bioinformatics tool was implemented for functional annotation analyses on the detected CpGs. The identified CpGs were further tested in an independent cohort. For the CpGs replicated in the independent cohort, linear mixed models were applied to assess the association of DNA methylation with low-density lipoprotein (LDL) at different ages (2, 5, 8, 11 and 14 years). Results In total, 579 out of 385,183 CpGs were identified after adjusting for multiple testing (FDR = 0.05), of which ~60% were positively associated with arsenic exposure. Functional annotation analysis on these CpGs detected 17 KEGG pathways (FDR = 0.05) including pathways for cardiovascular diseases (CVD) and diabetes mellitus. In the independent cohort, about 46% (252 out of 553 CpGs) of the identified CpGs showed associations consistent with those in the study cohort. In total, 11 CpGs replicated in the independent cohort were in the pathways related to CVD and diabetes mellitus. Via longitudinal analyses, we found at 5 out of the 11 CpGs methylation was associated with LDL over time and interactions between DNA methylation and time were observed at 4 of the 5 CpGs, cg25189764 (coeff = 0.157, p-value = 0.047), cg04986899 (coeff. For interaction [coeff.int] = 0.030, p-value = 0.024), cg04903360 (coeff.int = 0.026, p-value = 0.032), cg08198265 (coeff.int = −0.063, p-value = 0.0021), cg10473311 (coeff.int = −0.021, p-value = 0.027). Conclusion In utero arsenic exposure was associated with cord blood DNA methylation at various CpGs. The identified CpGs may help determine pathological epigenetic mechanisms linked to in utero arsenic exposure. Five CpGs (cg25189764, cg04986899, cg04903360, cg08198265 and cg10473311) may serve as epigenetic markers for changes in LDL later in life.http://link.springer.com/article/10.1186/s12940-017-0262-0ArsenicDNA methylationCpGDAVIDKEGG pathwayGenome-wide |
| spellingShingle | Akhilesh Kaushal Hongmei Zhang Wilfried J. J. Karmaus Todd M. Everson Carmen J. Marsit Margaret R. Karagas Shih-Fen Tsai Hui-Ju Wen Shu-Li Wang Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life Environmental Health Arsenic DNA methylation CpG DAVID KEGG pathway Genome-wide |
| title | Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life |
| title_full | Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life |
| title_fullStr | Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life |
| title_full_unstemmed | Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life |
| title_short | Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life |
| title_sort | genome wide dna methylation at birth in relation to in utero arsenic exposure and the associated health in later life |
| topic | Arsenic DNA methylation CpG DAVID KEGG pathway Genome-wide |
| url | http://link.springer.com/article/10.1186/s12940-017-0262-0 |
| work_keys_str_mv | AT akhileshkaushal genomewidednamethylationatbirthinrelationtoinuteroarsenicexposureandtheassociatedhealthinlaterlife AT hongmeizhang genomewidednamethylationatbirthinrelationtoinuteroarsenicexposureandtheassociatedhealthinlaterlife AT wilfriedjjkarmaus genomewidednamethylationatbirthinrelationtoinuteroarsenicexposureandtheassociatedhealthinlaterlife AT toddmeverson genomewidednamethylationatbirthinrelationtoinuteroarsenicexposureandtheassociatedhealthinlaterlife AT carmenjmarsit genomewidednamethylationatbirthinrelationtoinuteroarsenicexposureandtheassociatedhealthinlaterlife AT margaretrkaragas genomewidednamethylationatbirthinrelationtoinuteroarsenicexposureandtheassociatedhealthinlaterlife AT shihfentsai genomewidednamethylationatbirthinrelationtoinuteroarsenicexposureandtheassociatedhealthinlaterlife AT huijuwen genomewidednamethylationatbirthinrelationtoinuteroarsenicexposureandtheassociatedhealthinlaterlife AT shuliwang genomewidednamethylationatbirthinrelationtoinuteroarsenicexposureandtheassociatedhealthinlaterlife |