Exposure to arsenic at different life-stages and DNA methylation meta-analysis in buccal cells and leukocytes

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dc.contributor.authorBozack, Anne K.
dc.contributor.authorBoileau, Philippe
dc.contributor.authorWei, Linqing
dc.contributor.authorHubbard, Alan E.
dc.contributor.authorSillé, Fenna C. M.
dc.contributor.authorFerreccio Readi, Catterina
dc.contributor.authorAcevedo Romo, Johanna Patricia
dc.contributor.authorHou, Lifang
dc.contributor.authorIlievski, Vesna
dc.contributor.authorSteinmaus, Craig
dc.contributor.authorBozack, Anne K.
dc.contributor.authorBoileau, Philippe
dc.contributor.authorWei, Linqing
dc.contributor.authorHubbard, Alan E.
dc.contributor.authorSillé, Fenna C. M.
dc.contributor.authorFerreccio Readi, Catterina
dc.contributor.authorAcevedo Romo, Johanna Patricia
dc.contributor.authorHou, Lifang
dc.contributor.authorIlievski, Vesna
dc.contributor.authorSteinmaus, Craig
dc.date.accessioned2021-07-15T12:18:02Z
dc.date.available2021-07-15T12:18:02Z
dc.date.issued2021
dc.date.updated2021-07-11T00:02:17Z
dc.description.abstractAbstract Background Arsenic (As) exposure through drinking water is a global public health concern. Epigenetic dysregulation including changes in DNA methylation (DNAm), may be involved in arsenic toxicity. Epigenome-wide association studies (EWAS) of arsenic exposure have been restricted to single populations and comparison across EWAS has been limited by methodological differences. Leveraging data from epidemiological studies conducted in Chile and Bangladesh, we use a harmonized data processing and analysis pipeline and meta-analysis to combine results from four EWAS. Methods DNAm was measured among adults in Chile with and without prenatal and early-life As exposure in PBMCs and buccal cells (N = 40, 850K array) and among men in Bangladesh with high and low As exposure in PBMCs (N = 32, 850K array; N = 48, 450K array). Linear models were used to identify differentially methylated positions (DMPs) and differentially variable positions (DVPs) adjusting for age, smoking, cell type, and sex in the Chile cohort. Probes common across EWAS were meta-analyzed using METAL, and differentially methylated and variable regions (DMRs and DVRs, respectively) were identified using comb-p. KEGG pathway analysis was used to understand biological functions of DMPs and DVPs. Results In a meta-analysis restricted to PBMCs, we identified one DMP and 23 DVPs associated with arsenic exposure; including buccal cells, we identified 3 DMPs and 19 DVPs (FDR < 0.05). Using meta-analyzed results, we identified 11 DMRs and 11 DVRs in PBMC samples, and 16 DMRs and 19 DVRs in PBMC and buccal cell samples. One region annotated to LRRC27 was identified as a DMR and DVR. Arsenic-associated KEGG pathways included lysosome, autophagy, and mTOR signaling, AMPK signaling, and one carbon pool by folate. Conclusions Using a two-step process of (1) harmonized data processing and analysis and (2) meta-analysis, we leverage four DNAm datasets from two continents of individuals exposed to high levels of As prenatally and during adulthood to identify DMPs and DVPs associated with arsenic exposure. Our approach suggests that standardizing analytical pipelines can aid in identifying biological meaningful signals.
dc.format.extent18 páginas
dc.fuente.origenAutoarchivo
dc.identifier.citationEnvironmental Health. 2021 Jul 09;20(1):79
dc.identifier.doi10.1186/s12940-021-00754-7
dc.identifier.urihttps://doi.org/10.1186/s12940-021-00754-7
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/60987
dc.identifier.wosidWOS:000671560400001
dc.information.autorucEscuela de Medicina ; Ferreccio Readi, Catterine ; S/I ; 99684
dc.information.autorucEscuela de Medicina ; Acevedo Romo, Johanna Patricia ; 0000-0002-6341-1865 ; 15543
dc.issue.numeroNo. 79
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final18
dc.pagina.inicio1
dc.revistaEnvironmental Healthes_ES
dc.rightsacceso abierto
dc.rights.holderThe Author(s)
dc.subjectArsenices_ES
dc.subjectDNA methylationes_ES
dc.subjectEpigeneticses_ES
dc.subjectPrenatal exposurees_ES
dc.subject.ddc615.925715
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods06 Clean water and sanitation
dc.subject.odspa06 Agua limpia y saneamiento
dc.titleExposure to arsenic at different life-stages and DNA methylation meta-analysis in buccal cells and leukocyteses_ES
dc.typeartículo
dc.volumenVol. 20
sipa.codpersvinculados99684
sipa.codpersvinculados15543
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