First evidence of association between past environmental exposure to dioxin and DNA methylation of CYP1A1 and IGF2 genes in present day Vietnamese population

Giuliani, Cristina; Biggs, David; Nguyen, Thi Thanh Tam; Marasco, Elena; Fanti, Sara De; Garagnani, Paolo; Phan, Minh Triet Le; Nguyen, Viet Nhan; Luiselli, Donata; Romeo, Giovanni

doi:10.1016/j.envpol.2018.07.015

Cited by 21 publications

(7 citation statements)

References 51 publications

(65 reference statements)

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“…We carried out additional analysis with the whole blood data for differentially methylated loci within the genes IGF2 and CYP1A1, which were targeted in a study of the peripheral blood of a group of people living in areas of Vietnam which were sprayed with Agent Orange [39]. Giuliani et al, 2018 provide evidence that loci within CYP1A1, but not IGF2, were altered with Agent Orange exposure.…”

Section: Resultsmentioning

confidence: 99%

“…We identi ed the 116 signi cantly methylated CpG loci with dioxin exposure at the 5% FDR level in the AFHS data [17], and subsequently, performed t-tests comparing methylation levels in the high burden group compared to the controls. Another study targeted CYP1A1 and IGF2 in a candidate-gene analysis of the whole blood of Vietnamese individuals potentially exposed to Agent Orange [39]. At each of the CpGs within CYP1A1 and IGF2 in the AFHS whole blood 450K data, we executed a t-test to compare methylation levels between the highly burdened group and the controls.…”

Section: Methodsmentioning

confidence: 99%

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DNA Methylation in the Adipose Tissue and Whole Blood of Agent Orange-exposed Operation Ranch Hand Veterans

Rytel

Butler

Eliot

et al. 2020

Preprint

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BackgroundBetween 1962 and 1971, the US Air Force sprayed Agent Orange across Vietnam, exposing many soldiers to this dioxin-containing herbicide. Several negative health outcomes have been linked to Agent Orange exposure, but data is lacking on the effects this chemical has on the genome. Therefore, we sought to characterize the impact of Agent Orange exposure on DNA methylation in the whole blood and adipose tissue of veterans enrolled in the Air Force Health Study (AFHS). MethodsWe received adipose tissue (n=37) and whole blood (n=42) from veterans in the AFHS. Study participants were grouped as having low, moderate, or high TCDD body burden based on their previously measured serum levels of dioxin. DNA methylation was assessed using the Illumina 450K platform.ResultsEpigenome-wide analysis indicated that there were no FDR-significantly methylated CpGs in either tissue with TCDD burden. However, 3 CpGs in the adipose tissue (contained within SLC9A3, LYNX1, and TNRC18) were marginally significantly (q<0.1) hypomethylated, and 1 CpG in whole blood (contained within PTPRN2) was marginally significantly (q<0.1) hypermethylated with high TCDD burden. Analysis for differentially methylated DNA regions yielded SLC9A3, among other regions in adipose tissue, to be significantly differentially methylated with higher TCDD burden. Comparing whole blood data to a study of dioxin exposed adults from Alabama identified a CpG within the gene SMO that was hypomethylated with dioxin exposure in both studies. ConclusionWe found limited evidence of dioxin associated DNA methylation in adipose tissue and whole blood in this pilot study of Vietnam War veterans. Nevertheless, loci in the genes of SLC9A3 in adipose tissue, and PTPRN2 and SMO in whole blood, should be included in future exposure analyses.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

DNA Methylation in the Adipose Tissue and Whole Blood of Agent Orange-exposed Operation Ranch Hand Veterans

Rytel

Butler

Eliot

et al. 2020

Preprint

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“…Researchers found mutations that occurred in spermiogenesis that impacted the health of their progeny, including leukemias. 56,57 Tabaco smoke exposure is well studied in humans and transgenerational effects are recognized. 58 Strengths And Limitations…”

Section: Discussionmentioning

confidence: 99%

Evidence of Transgenerational Effects on Autism Spectrum Disorder Using Multigenerational Space-Time Cluster Detection

Steed

Bakian

Smith

et al. 2022

Preprint

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Background Transgenerational epigenetic risks associated with complex health outcomes, such as autism spectrum disorder (ASD), have attracted increasing attention. Transgenerational environmental risk exposures with potential for epigenetic effects can be effectively identified using space-time clustering. Specifically applied to ancestors of individuals with disease outcomes, space-time clustering characterized for vulnerable developmental stages of growth can provide a measure of relative risk for disease outcomes in descendants. Objectives (1) Identify space-time clusters of ancestors with a descendent with a clinical ASD diagnosis and matched controls. (2) Identify developmental windows of ancestors with the highest relative risk for ASD in descendants. (3) Identify how the relative risk may vary through the maternal or paternal line. Methods Family pedigrees linked to residential locations of ASD cases in Utah have been used to identify space-time clusters of ancestors. Control family pedigrees of none-cases based on age and sex have been matched to cases 2:1. The data have been categorized by maternal or paternal lineage at birth, childhood, and adolescence. A total of 3,957 children, both parents, and maternal and paternal grandparents were identified. Bernoulli space-time binomial relative risk (RR) scan statistic was used to identify clusters. Monte Carlo simulation was used for statistical significance testing. Results Twenty statistically significant clusters were identified. Thirteen increased RR (> 1.0) space-time clusters were identified from the maternal and paternal lines at a p-value < 0.05. The paternal grandparents carry the greatest RR (2.86–2.96) during birth and childhood in the 1950’s -1960, which represent the smallest size clusters, and occur in urban areas. Additionally, seven statistically significant clusters with RR < 1 were relatively large in area, covering more rural areas of the state. Conclusion This study has identified statistically significant space-time clusters during critical developmental windows that are associated with ASD risk in descendants. The geographic space and time clusters family pedigrees with over 3 + generations, which we refer to as a person’s geographic legacy, is a powerful tool for studying transgenerational effects that may be epigenetic in nature. Our novel use of space-time clustering can be applied to any disease where family pedigree data is available.

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“…Another notable example is the investigation into grandparent exposure to dioxin TCDD, an herbicide used in the Vietnam War as a chemical agent. Researchers found mutations that occurred in spermiogenesis that impacted the health of their progeny, including leukemias [ 54 , 55 ]. Tabaco smoke exposure is well studied in humans and transgenerational effects are recognized [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Evidence of transgenerational effects on autism spectrum disorder using multigenerational space-time cluster detection

et al. 2022

View full text Add to dashboard Cite

Background Transgenerational epigenetic risks associated with complex health outcomes, such as autism spectrum disorder (ASD), have attracted increasing attention. Transgenerational environmental risk exposures with potential for epigenetic effects can be effectively identified using space-time clustering. Specifically applied to ancestors of individuals with disease outcomes, space-time clustering characterized for vulnerable developmental stages of growth can provide a measure of relative risk for disease outcomes in descendants. Objectives (1) Identify space-time clusters of ancestors with a descendent with a clinical ASD diagnosis and matched controls. (2) Identify developmental windows of ancestors with the highest relative risk for ASD in descendants. (3) Identify how the relative risk may vary through the maternal or paternal line. Methods Family pedigrees linked to residential locations of ASD cases in Utah have been used to identify space-time clusters of ancestors. Control family pedigrees of none-cases based on age and sex have been matched to cases 2:1. The data have been categorized by maternal or paternal lineage at birth, childhood, and adolescence. A total of 3957 children, both parents, and maternal and paternal grandparents were identified. Bernoulli space-time binomial relative risk (RR) scan statistic was used to identify clusters. Monte Carlo simulation was used for statistical significance testing. Results Twenty statistically significant clusters were identified. Thirteen increased RR (> 1.0) space-time clusters were identified from the maternal and paternal lines at a p-value < 0.05. The paternal grandparents carry the greatest RR (2.86–2.96) during birth and childhood in the 1950’s–1960, which represent the smallest size clusters, and occur in urban areas. Additionally, seven statistically significant clusters with RR < 1 were relatively large in area, covering more rural areas of the state. Conclusion This study has identified statistically significant space-time clusters during critical developmental windows that are associated with ASD risk in descendants. The geographic space and time clusters family pedigrees with over 3 + generations, which we refer to as a person’s geographic legacy, is a powerful tool for studying transgenerational effects that may be epigenetic in nature. Our novel use of space-time clustering can be applied to any disease where family pedigree data is available.

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First evidence of association between past environmental exposure to dioxin and DNA methylation of CYP1A1 and IGF2 genes in present day Vietnamese population

Cited by 21 publications

References 51 publications

DNA Methylation in the Adipose Tissue and Whole Blood of Agent Orange-exposed Operation Ranch Hand Veterans

DNA Methylation in the Adipose Tissue and Whole Blood of Agent Orange-exposed Operation Ranch Hand Veterans

Evidence of Transgenerational Effects on Autism Spectrum Disorder Using Multigenerational Space-Time Cluster Detection

Evidence of transgenerational effects on autism spectrum disorder using multigenerational space-time cluster detection

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