The Experts below are selected from a list of 159 Experts worldwide ranked by ideXlab platform
Karen N. Conneely - One of the best experts on this subject based on the ideXlab platform.
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Sex-specific DNA methylation differences in people exposed to Polybrominated Biphenyl.
Epigenomics, 2020Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, M. Elizabeth Marder, Carmen J. Marsit, Michele Marcus, Dana B Barr, Sabrina A Gerkowicz, Karen N. ConneelyAbstract:Aim: Michigan residents were exposed to Polybrominated Biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate
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sex specific dna methylation differences in people exposed to Polybrominated Biphenyl
Epigenomics, 2020Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, Carmen J. Marsit, Michele Marcus, Elizabeth M. Marder, Dana B Barr, Sabrina A Gerkowicz, Karen N. ConneelyAbstract:Aim: Michigan residents were exposed to Polybrominated Biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate <0.05). No CpGs were associated in both sexes. These CpGs were enriched in different functional regions and transcription factor binding sites in each sex. Conclusion: Exposure to PBBs may have sex-specific effects on the epigenome that may underlie sex-specific adverse health outcomes.
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endometriosis endocrine disrupters and epigenetics an investigation into the complex interplay in women with Polybrominated Biphenyl exposure and endometriosis
Journal of Assisted Reproduction and Genetics, 2020Co-Authors: Sabrina A Gerkowicz, Sarah W. Curtis, Dawayland O. Cobb, Metrecia L. Terrell, Michele Marcus, Karen N. Conneely, Anna K Knight, Jessica B Spencer, Alica K SmithAbstract:PURPOSE Endocrine disrupting compounds (EDCs) have been shown to affect multiple biologic processes especially steroid-hormone processes. We sought to determine differences in DNA methylation exists between women with and without endometriosis following exposure to Polybrominated Biphenyl (PBB). METHODS Cross-sectional study of 305 females in the Michigan PBB Registry. DNA was extracted, and DNA methylation was interrogated using the MethylationEPIC BeadChip (Illumina, San Diego, California). Demographic data was analyzed using Chi-squared and T tests. Linear regressions were performed for each cytosine-guanine dinucleotide (CpG) site, modeling the logit transformation of the β value as a linear function of the presence of endometriosis. Sensitivity analyses were conducted controlling for estradiol levels and menopausal status. Replication study performed evaluating for any association between CpGs reported in the literature and our findings. RESULTS In total, 39,877 CpGs nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity, although none remained significant after correction for multiple comparisons (FDR < 0.05). Pathway analysis of these CpGs showed enrichment in 68 biologic pathways involved in various endocrine, immunologic, oncologic, and cell regulation processes as well as embryologic reproductive tract development and function (FoxO, Wnt, and Hedgehog signaling). We identified 42,261 CpG sites in the literature reported to be associated with endometriosis; 2012 of these CpG sites were also significant in our cohort. CONCLUSION We found 39,877 CpG sites that nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity; however, none remained significant after correction for multiple comparisons (FDR < 0.05).
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environmental exposure to Polybrominated Biphenyl pbb associates with an increased rate of biological aging
Aging (Albany NY), 2019Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, Carmen J. Marsit, Michele Marcus, Karen N. Conneely, Elizabeth M. Marder, Dana B Barr, Alicia K. SmithAbstract:Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently measured through DNA methylation) can be older than chronological age. Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like Polybrominated Biphenyl (PBB) would associate with age acceleration. Three different epigenetic age acceleration measures (intrinsic, extrinsic, and phenotypic) were calculated from existing epigenetic data in whole blood from a population highly exposed to PBB (N=658). Association between serum PBB concentration and these measures was tested, controlling for sex, lipid levels, and estimated cell type proportions. Higher PBB levels associated with increased age acceleration (intrinsic: β=0.24, 95%CI=0.01-0.46, p = 0.03; extrinsic: β=0.39, 95%CI=0.12-0.65, p = 0.004; and phenotypic: β=0.30, 95%CI=0.05-0.54, p = 0.01). Neither age when exposed to PBB nor sex statistically interacted with PBB to predict age acceleration, but, in stratified analyses, the association between PBB and age acceleration was only in people exposed before finishing puberty and in men. This suggests that EDCs can associate with the biological aging process, and further studies are warranted to investigate other environmental pollutants' effect on aging.
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exposure to Polybrominated Biphenyl and stochastic epigenetic mutations application of a novel epigenetic approach to environmental exposure in the michigan Polybrominated Biphenyl registry
Epigenetics, 2019Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, Carmen J. Marsit, Michele Marcus, Karen N. Conneely, Elizabeth M. Marder, Dana B Barr, Alicia K. SmithAbstract:Endocrine-disrupting compounds are associated with altered epigenetic regulation and adverse health outcomes, although inconsistent results suggest that people have varied responses to the same exposure. Interpersonal variation in response to environmental exposures is not identified using standard, population-based methods. However, methods that capture an individual's response, such as analyzing stochastic epigenetic mutations (SEMs), may capture currently missed effects of environmental exposure. To test whether Polybrominated Biphenyl (PBB) was associated with SEMs, DNA methylation was measured using Illumina's MethylationEPIC array in PBB-exposed individuals, and SEMs were identified. Association was tested using a linear regression with robust sandwich variance estimators, controlling for age, sex, lipids, and cell types. The number of SEMs was variable (range: 119-18,309), and positively associated with age (p = 1.23e-17), but not with sex (p = 0.97). PBBs and SEMs were only positively associated in people who were older when they were exposed (p = 0.02 vs. p = 0.91). Many subjects had SEMs enriched in biological pathways, particularly in pathways involved with xenobiotic metabolism and endocrine function. Higher number of SEMs was also associated with higher age acceleration (intrinsic: p = 1.70e-3; extrinsic: p = 3.59e-11), indicating that SEMs may be associated with age-related health problems. Finding an association between environmental contaminants and higher SEMs may provide insight into individual differences in response to environmental contaminants, as well as into the biological mechanism behind SEM formation. Furthermore, these results suggest that people may be particularly vulnerable to epigenetic dysregulation from environmental exposures as they age.
Michele Marcus - One of the best experts on this subject based on the ideXlab platform.
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sex specific dna methylation differences in people exposed to Polybrominated Biphenyl
Epigenomics, 2020Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, Carmen J. Marsit, Michele Marcus, Elizabeth M. Marder, Dana B Barr, Sabrina A Gerkowicz, Karen N. ConneelyAbstract:Aim: Michigan residents were exposed to Polybrominated Biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate <0.05). No CpGs were associated in both sexes. These CpGs were enriched in different functional regions and transcription factor binding sites in each sex. Conclusion: Exposure to PBBs may have sex-specific effects on the epigenome that may underlie sex-specific adverse health outcomes.
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Sex-specific DNA methylation differences in people exposed to Polybrominated Biphenyl.
Epigenomics, 2020Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, M. Elizabeth Marder, Carmen J. Marsit, Michele Marcus, Dana B Barr, Sabrina A Gerkowicz, Karen N. ConneelyAbstract:Aim: Michigan residents were exposed to Polybrominated Biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate
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examining reproductive health outcomes in females exposed to polychlorinated Biphenyl and Polybrominated Biphenyl
Scientific Reports, 2020Co-Authors: Michael F Neblett, Sarah W. Curtis, Metrecia L. Terrell, Michele Marcus, Elizabeth M. Marder, Dana B Barr, Sabrina A Gerkowicz, Jessica B Spencer, Victoria S Jiang, Alicia K. SmithAbstract:In 1973, accidental contamination of Michigan livestock with Polybrominated Biphenyls (PBBs) led to the establishment of a registry of exposed individuals that have been followed for > 40 years. Besides being exposed to PBBs, this cohort has also been exposed to polychlorinated Biphenyls (PCBs), a structurally similar class of environmental pollutants, at levels similar to average US exposure. In this study, we examined the association between current serum PCB and PBB levels and various female reproductive health outcomes to build upon previous work and inconsistencies. Participation in this cross-sectional study required a blood draw and completion of a detailed health questionnaire. Analysis included only female participants who had participated between 2012 and 2015 (N = 254). Multivariate linear and logistic regression models were used to identify associations between serum PCB and PBB levels with each gynecological and infertility outcome. Additionally, a generalized estimating equation (GEE) model was used to evaluate each pregnancy and birth outcome in order to account for multiple pregnancies per woman. We controlled for age, body mass index, and total lipid levels in all analyses. A p-value of <0.05 was used for statistical significance. Among the women who reported ever being pregnant, there was a significant negative association with higher total PCB levels associating with fewer lifetime pregnancies ( β = −0.11, 95% CI = −0.21 to −0.005, p = 0.04). There were no correlations between serum PCB levels and the self-reported gynecological outcomes (pelvic inflammatory disease, endometriosis, polycystic ovarian syndrome, or uterine fibroids). No associations were identified between serum PCB levels and the prevalence of female infertility in women reporting ever having sexual intercourse with a male partner. There were no associations identified between serum PCB levels and pregnancy outcomes (singleton live births or miscarriages) or birth outcomes (preterm birth, birth weight, birth defects, hypertensive disorders of pregnancy, or gestational diabetes). PBB was not associated with any outcome. Further research is needed to determine if and how PCB may reduce pregnancy number.
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endometriosis endocrine disrupters and epigenetics an investigation into the complex interplay in women with Polybrominated Biphenyl exposure and endometriosis
Journal of Assisted Reproduction and Genetics, 2020Co-Authors: Sabrina A Gerkowicz, Sarah W. Curtis, Dawayland O. Cobb, Metrecia L. Terrell, Michele Marcus, Karen N. Conneely, Anna K Knight, Jessica B Spencer, Alica K SmithAbstract:PURPOSE Endocrine disrupting compounds (EDCs) have been shown to affect multiple biologic processes especially steroid-hormone processes. We sought to determine differences in DNA methylation exists between women with and without endometriosis following exposure to Polybrominated Biphenyl (PBB). METHODS Cross-sectional study of 305 females in the Michigan PBB Registry. DNA was extracted, and DNA methylation was interrogated using the MethylationEPIC BeadChip (Illumina, San Diego, California). Demographic data was analyzed using Chi-squared and T tests. Linear regressions were performed for each cytosine-guanine dinucleotide (CpG) site, modeling the logit transformation of the β value as a linear function of the presence of endometriosis. Sensitivity analyses were conducted controlling for estradiol levels and menopausal status. Replication study performed evaluating for any association between CpGs reported in the literature and our findings. RESULTS In total, 39,877 CpGs nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity, although none remained significant after correction for multiple comparisons (FDR < 0.05). Pathway analysis of these CpGs showed enrichment in 68 biologic pathways involved in various endocrine, immunologic, oncologic, and cell regulation processes as well as embryologic reproductive tract development and function (FoxO, Wnt, and Hedgehog signaling). We identified 42,261 CpG sites in the literature reported to be associated with endometriosis; 2012 of these CpG sites were also significant in our cohort. CONCLUSION We found 39,877 CpG sites that nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity; however, none remained significant after correction for multiple comparisons (FDR < 0.05).
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environmental exposure to Polybrominated Biphenyl pbb associates with an increased rate of biological aging
Aging (Albany NY), 2019Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, Carmen J. Marsit, Michele Marcus, Karen N. Conneely, Elizabeth M. Marder, Dana B Barr, Alicia K. SmithAbstract:Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently measured through DNA methylation) can be older than chronological age. Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like Polybrominated Biphenyl (PBB) would associate with age acceleration. Three different epigenetic age acceleration measures (intrinsic, extrinsic, and phenotypic) were calculated from existing epigenetic data in whole blood from a population highly exposed to PBB (N=658). Association between serum PBB concentration and these measures was tested, controlling for sex, lipid levels, and estimated cell type proportions. Higher PBB levels associated with increased age acceleration (intrinsic: β=0.24, 95%CI=0.01-0.46, p = 0.03; extrinsic: β=0.39, 95%CI=0.12-0.65, p = 0.004; and phenotypic: β=0.30, 95%CI=0.05-0.54, p = 0.01). Neither age when exposed to PBB nor sex statistically interacted with PBB to predict age acceleration, but, in stratified analyses, the association between PBB and age acceleration was only in people exposed before finishing puberty and in men. This suggests that EDCs can associate with the biological aging process, and further studies are warranted to investigate other environmental pollutants' effect on aging.
Sarah W. Curtis - One of the best experts on this subject based on the ideXlab platform.
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Sex-specific DNA methylation differences in people exposed to Polybrominated Biphenyl.
Epigenomics, 2020Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, M. Elizabeth Marder, Carmen J. Marsit, Michele Marcus, Dana B Barr, Sabrina A Gerkowicz, Karen N. ConneelyAbstract:Aim: Michigan residents were exposed to Polybrominated Biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate
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sex specific dna methylation differences in people exposed to Polybrominated Biphenyl
Epigenomics, 2020Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, Carmen J. Marsit, Michele Marcus, Elizabeth M. Marder, Dana B Barr, Sabrina A Gerkowicz, Karen N. ConneelyAbstract:Aim: Michigan residents were exposed to Polybrominated Biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate <0.05). No CpGs were associated in both sexes. These CpGs were enriched in different functional regions and transcription factor binding sites in each sex. Conclusion: Exposure to PBBs may have sex-specific effects on the epigenome that may underlie sex-specific adverse health outcomes.
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examining reproductive health outcomes in females exposed to polychlorinated Biphenyl and Polybrominated Biphenyl
Scientific Reports, 2020Co-Authors: Michael F Neblett, Sarah W. Curtis, Metrecia L. Terrell, Michele Marcus, Elizabeth M. Marder, Dana B Barr, Sabrina A Gerkowicz, Jessica B Spencer, Victoria S Jiang, Alicia K. SmithAbstract:In 1973, accidental contamination of Michigan livestock with Polybrominated Biphenyls (PBBs) led to the establishment of a registry of exposed individuals that have been followed for > 40 years. Besides being exposed to PBBs, this cohort has also been exposed to polychlorinated Biphenyls (PCBs), a structurally similar class of environmental pollutants, at levels similar to average US exposure. In this study, we examined the association between current serum PCB and PBB levels and various female reproductive health outcomes to build upon previous work and inconsistencies. Participation in this cross-sectional study required a blood draw and completion of a detailed health questionnaire. Analysis included only female participants who had participated between 2012 and 2015 (N = 254). Multivariate linear and logistic regression models were used to identify associations between serum PCB and PBB levels with each gynecological and infertility outcome. Additionally, a generalized estimating equation (GEE) model was used to evaluate each pregnancy and birth outcome in order to account for multiple pregnancies per woman. We controlled for age, body mass index, and total lipid levels in all analyses. A p-value of <0.05 was used for statistical significance. Among the women who reported ever being pregnant, there was a significant negative association with higher total PCB levels associating with fewer lifetime pregnancies ( β = −0.11, 95% CI = −0.21 to −0.005, p = 0.04). There were no correlations between serum PCB levels and the self-reported gynecological outcomes (pelvic inflammatory disease, endometriosis, polycystic ovarian syndrome, or uterine fibroids). No associations were identified between serum PCB levels and the prevalence of female infertility in women reporting ever having sexual intercourse with a male partner. There were no associations identified between serum PCB levels and pregnancy outcomes (singleton live births or miscarriages) or birth outcomes (preterm birth, birth weight, birth defects, hypertensive disorders of pregnancy, or gestational diabetes). PBB was not associated with any outcome. Further research is needed to determine if and how PCB may reduce pregnancy number.
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endometriosis endocrine disrupters and epigenetics an investigation into the complex interplay in women with Polybrominated Biphenyl exposure and endometriosis
Journal of Assisted Reproduction and Genetics, 2020Co-Authors: Sabrina A Gerkowicz, Sarah W. Curtis, Dawayland O. Cobb, Metrecia L. Terrell, Michele Marcus, Karen N. Conneely, Anna K Knight, Jessica B Spencer, Alica K SmithAbstract:PURPOSE Endocrine disrupting compounds (EDCs) have been shown to affect multiple biologic processes especially steroid-hormone processes. We sought to determine differences in DNA methylation exists between women with and without endometriosis following exposure to Polybrominated Biphenyl (PBB). METHODS Cross-sectional study of 305 females in the Michigan PBB Registry. DNA was extracted, and DNA methylation was interrogated using the MethylationEPIC BeadChip (Illumina, San Diego, California). Demographic data was analyzed using Chi-squared and T tests. Linear regressions were performed for each cytosine-guanine dinucleotide (CpG) site, modeling the logit transformation of the β value as a linear function of the presence of endometriosis. Sensitivity analyses were conducted controlling for estradiol levels and menopausal status. Replication study performed evaluating for any association between CpGs reported in the literature and our findings. RESULTS In total, 39,877 CpGs nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity, although none remained significant after correction for multiple comparisons (FDR < 0.05). Pathway analysis of these CpGs showed enrichment in 68 biologic pathways involved in various endocrine, immunologic, oncologic, and cell regulation processes as well as embryologic reproductive tract development and function (FoxO, Wnt, and Hedgehog signaling). We identified 42,261 CpG sites in the literature reported to be associated with endometriosis; 2012 of these CpG sites were also significant in our cohort. CONCLUSION We found 39,877 CpG sites that nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity; however, none remained significant after correction for multiple comparisons (FDR < 0.05).
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environmental exposure to Polybrominated Biphenyl pbb associates with an increased rate of biological aging
Aging (Albany NY), 2019Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, Carmen J. Marsit, Michele Marcus, Karen N. Conneely, Elizabeth M. Marder, Dana B Barr, Alicia K. SmithAbstract:Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently measured through DNA methylation) can be older than chronological age. Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like Polybrominated Biphenyl (PBB) would associate with age acceleration. Three different epigenetic age acceleration measures (intrinsic, extrinsic, and phenotypic) were calculated from existing epigenetic data in whole blood from a population highly exposed to PBB (N=658). Association between serum PBB concentration and these measures was tested, controlling for sex, lipid levels, and estimated cell type proportions. Higher PBB levels associated with increased age acceleration (intrinsic: β=0.24, 95%CI=0.01-0.46, p = 0.03; extrinsic: β=0.39, 95%CI=0.12-0.65, p = 0.004; and phenotypic: β=0.30, 95%CI=0.05-0.54, p = 0.01). Neither age when exposed to PBB nor sex statistically interacted with PBB to predict age acceleration, but, in stratified analyses, the association between PBB and age acceleration was only in people exposed before finishing puberty and in men. This suggests that EDCs can associate with the biological aging process, and further studies are warranted to investigate other environmental pollutants' effect on aging.
Metrecia L. Terrell - One of the best experts on this subject based on the ideXlab platform.
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Sex-specific DNA methylation differences in people exposed to Polybrominated Biphenyl.
Epigenomics, 2020Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, M. Elizabeth Marder, Carmen J. Marsit, Michele Marcus, Dana B Barr, Sabrina A Gerkowicz, Karen N. ConneelyAbstract:Aim: Michigan residents were exposed to Polybrominated Biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate
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sex specific dna methylation differences in people exposed to Polybrominated Biphenyl
Epigenomics, 2020Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, Carmen J. Marsit, Michele Marcus, Elizabeth M. Marder, Dana B Barr, Sabrina A Gerkowicz, Karen N. ConneelyAbstract:Aim: Michigan residents were exposed to Polybrominated Biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate <0.05). No CpGs were associated in both sexes. These CpGs were enriched in different functional regions and transcription factor binding sites in each sex. Conclusion: Exposure to PBBs may have sex-specific effects on the epigenome that may underlie sex-specific adverse health outcomes.
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examining reproductive health outcomes in females exposed to polychlorinated Biphenyl and Polybrominated Biphenyl
Scientific Reports, 2020Co-Authors: Michael F Neblett, Sarah W. Curtis, Metrecia L. Terrell, Michele Marcus, Elizabeth M. Marder, Dana B Barr, Sabrina A Gerkowicz, Jessica B Spencer, Victoria S Jiang, Alicia K. SmithAbstract:In 1973, accidental contamination of Michigan livestock with Polybrominated Biphenyls (PBBs) led to the establishment of a registry of exposed individuals that have been followed for > 40 years. Besides being exposed to PBBs, this cohort has also been exposed to polychlorinated Biphenyls (PCBs), a structurally similar class of environmental pollutants, at levels similar to average US exposure. In this study, we examined the association between current serum PCB and PBB levels and various female reproductive health outcomes to build upon previous work and inconsistencies. Participation in this cross-sectional study required a blood draw and completion of a detailed health questionnaire. Analysis included only female participants who had participated between 2012 and 2015 (N = 254). Multivariate linear and logistic regression models were used to identify associations between serum PCB and PBB levels with each gynecological and infertility outcome. Additionally, a generalized estimating equation (GEE) model was used to evaluate each pregnancy and birth outcome in order to account for multiple pregnancies per woman. We controlled for age, body mass index, and total lipid levels in all analyses. A p-value of <0.05 was used for statistical significance. Among the women who reported ever being pregnant, there was a significant negative association with higher total PCB levels associating with fewer lifetime pregnancies ( β = −0.11, 95% CI = −0.21 to −0.005, p = 0.04). There were no correlations between serum PCB levels and the self-reported gynecological outcomes (pelvic inflammatory disease, endometriosis, polycystic ovarian syndrome, or uterine fibroids). No associations were identified between serum PCB levels and the prevalence of female infertility in women reporting ever having sexual intercourse with a male partner. There were no associations identified between serum PCB levels and pregnancy outcomes (singleton live births or miscarriages) or birth outcomes (preterm birth, birth weight, birth defects, hypertensive disorders of pregnancy, or gestational diabetes). PBB was not associated with any outcome. Further research is needed to determine if and how PCB may reduce pregnancy number.
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endometriosis endocrine disrupters and epigenetics an investigation into the complex interplay in women with Polybrominated Biphenyl exposure and endometriosis
Journal of Assisted Reproduction and Genetics, 2020Co-Authors: Sabrina A Gerkowicz, Sarah W. Curtis, Dawayland O. Cobb, Metrecia L. Terrell, Michele Marcus, Karen N. Conneely, Anna K Knight, Jessica B Spencer, Alica K SmithAbstract:PURPOSE Endocrine disrupting compounds (EDCs) have been shown to affect multiple biologic processes especially steroid-hormone processes. We sought to determine differences in DNA methylation exists between women with and without endometriosis following exposure to Polybrominated Biphenyl (PBB). METHODS Cross-sectional study of 305 females in the Michigan PBB Registry. DNA was extracted, and DNA methylation was interrogated using the MethylationEPIC BeadChip (Illumina, San Diego, California). Demographic data was analyzed using Chi-squared and T tests. Linear regressions were performed for each cytosine-guanine dinucleotide (CpG) site, modeling the logit transformation of the β value as a linear function of the presence of endometriosis. Sensitivity analyses were conducted controlling for estradiol levels and menopausal status. Replication study performed evaluating for any association between CpGs reported in the literature and our findings. RESULTS In total, 39,877 CpGs nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity, although none remained significant after correction for multiple comparisons (FDR < 0.05). Pathway analysis of these CpGs showed enrichment in 68 biologic pathways involved in various endocrine, immunologic, oncologic, and cell regulation processes as well as embryologic reproductive tract development and function (FoxO, Wnt, and Hedgehog signaling). We identified 42,261 CpG sites in the literature reported to be associated with endometriosis; 2012 of these CpG sites were also significant in our cohort. CONCLUSION We found 39,877 CpG sites that nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity; however, none remained significant after correction for multiple comparisons (FDR < 0.05).
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environmental exposure to Polybrominated Biphenyl pbb associates with an increased rate of biological aging
Aging (Albany NY), 2019Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, Carmen J. Marsit, Michele Marcus, Karen N. Conneely, Elizabeth M. Marder, Dana B Barr, Alicia K. SmithAbstract:Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently measured through DNA methylation) can be older than chronological age. Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like Polybrominated Biphenyl (PBB) would associate with age acceleration. Three different epigenetic age acceleration measures (intrinsic, extrinsic, and phenotypic) were calculated from existing epigenetic data in whole blood from a population highly exposed to PBB (N=658). Association between serum PBB concentration and these measures was tested, controlling for sex, lipid levels, and estimated cell type proportions. Higher PBB levels associated with increased age acceleration (intrinsic: β=0.24, 95%CI=0.01-0.46, p = 0.03; extrinsic: β=0.39, 95%CI=0.12-0.65, p = 0.004; and phenotypic: β=0.30, 95%CI=0.05-0.54, p = 0.01). Neither age when exposed to PBB nor sex statistically interacted with PBB to predict age acceleration, but, in stratified analyses, the association between PBB and age acceleration was only in people exposed before finishing puberty and in men. This suggests that EDCs can associate with the biological aging process, and further studies are warranted to investigate other environmental pollutants' effect on aging.
Dawayland O. Cobb - One of the best experts on this subject based on the ideXlab platform.
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sex specific dna methylation differences in people exposed to Polybrominated Biphenyl
Epigenomics, 2020Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, Carmen J. Marsit, Michele Marcus, Elizabeth M. Marder, Dana B Barr, Sabrina A Gerkowicz, Karen N. ConneelyAbstract:Aim: Michigan residents were exposed to Polybrominated Biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate <0.05). No CpGs were associated in both sexes. These CpGs were enriched in different functional regions and transcription factor binding sites in each sex. Conclusion: Exposure to PBBs may have sex-specific effects on the epigenome that may underlie sex-specific adverse health outcomes.
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Sex-specific DNA methylation differences in people exposed to Polybrominated Biphenyl.
Epigenomics, 2020Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, M. Elizabeth Marder, Carmen J. Marsit, Michele Marcus, Dana B Barr, Sabrina A Gerkowicz, Karen N. ConneelyAbstract:Aim: Michigan residents were exposed to Polybrominated Biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate
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endometriosis endocrine disrupters and epigenetics an investigation into the complex interplay in women with Polybrominated Biphenyl exposure and endometriosis
Journal of Assisted Reproduction and Genetics, 2020Co-Authors: Sabrina A Gerkowicz, Sarah W. Curtis, Dawayland O. Cobb, Metrecia L. Terrell, Michele Marcus, Karen N. Conneely, Anna K Knight, Jessica B Spencer, Alica K SmithAbstract:PURPOSE Endocrine disrupting compounds (EDCs) have been shown to affect multiple biologic processes especially steroid-hormone processes. We sought to determine differences in DNA methylation exists between women with and without endometriosis following exposure to Polybrominated Biphenyl (PBB). METHODS Cross-sectional study of 305 females in the Michigan PBB Registry. DNA was extracted, and DNA methylation was interrogated using the MethylationEPIC BeadChip (Illumina, San Diego, California). Demographic data was analyzed using Chi-squared and T tests. Linear regressions were performed for each cytosine-guanine dinucleotide (CpG) site, modeling the logit transformation of the β value as a linear function of the presence of endometriosis. Sensitivity analyses were conducted controlling for estradiol levels and menopausal status. Replication study performed evaluating for any association between CpGs reported in the literature and our findings. RESULTS In total, 39,877 CpGs nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity, although none remained significant after correction for multiple comparisons (FDR < 0.05). Pathway analysis of these CpGs showed enrichment in 68 biologic pathways involved in various endocrine, immunologic, oncologic, and cell regulation processes as well as embryologic reproductive tract development and function (FoxO, Wnt, and Hedgehog signaling). We identified 42,261 CpG sites in the literature reported to be associated with endometriosis; 2012 of these CpG sites were also significant in our cohort. CONCLUSION We found 39,877 CpG sites that nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity; however, none remained significant after correction for multiple comparisons (FDR < 0.05).
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environmental exposure to Polybrominated Biphenyl pbb associates with an increased rate of biological aging
Aging (Albany NY), 2019Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, Carmen J. Marsit, Michele Marcus, Karen N. Conneely, Elizabeth M. Marder, Dana B Barr, Alicia K. SmithAbstract:Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently measured through DNA methylation) can be older than chronological age. Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like Polybrominated Biphenyl (PBB) would associate with age acceleration. Three different epigenetic age acceleration measures (intrinsic, extrinsic, and phenotypic) were calculated from existing epigenetic data in whole blood from a population highly exposed to PBB (N=658). Association between serum PBB concentration and these measures was tested, controlling for sex, lipid levels, and estimated cell type proportions. Higher PBB levels associated with increased age acceleration (intrinsic: β=0.24, 95%CI=0.01-0.46, p = 0.03; extrinsic: β=0.39, 95%CI=0.12-0.65, p = 0.004; and phenotypic: β=0.30, 95%CI=0.05-0.54, p = 0.01). Neither age when exposed to PBB nor sex statistically interacted with PBB to predict age acceleration, but, in stratified analyses, the association between PBB and age acceleration was only in people exposed before finishing puberty and in men. This suggests that EDCs can associate with the biological aging process, and further studies are warranted to investigate other environmental pollutants' effect on aging.
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exposure to Polybrominated Biphenyl and stochastic epigenetic mutations application of a novel epigenetic approach to environmental exposure in the michigan Polybrominated Biphenyl registry
Epigenetics, 2019Co-Authors: Sarah W. Curtis, Dawayland O. Cobb, Varun Kilaru, Metrecia L. Terrell, Carmen J. Marsit, Michele Marcus, Karen N. Conneely, Elizabeth M. Marder, Dana B Barr, Alicia K. SmithAbstract:Endocrine-disrupting compounds are associated with altered epigenetic regulation and adverse health outcomes, although inconsistent results suggest that people have varied responses to the same exposure. Interpersonal variation in response to environmental exposures is not identified using standard, population-based methods. However, methods that capture an individual's response, such as analyzing stochastic epigenetic mutations (SEMs), may capture currently missed effects of environmental exposure. To test whether Polybrominated Biphenyl (PBB) was associated with SEMs, DNA methylation was measured using Illumina's MethylationEPIC array in PBB-exposed individuals, and SEMs were identified. Association was tested using a linear regression with robust sandwich variance estimators, controlling for age, sex, lipids, and cell types. The number of SEMs was variable (range: 119-18,309), and positively associated with age (p = 1.23e-17), but not with sex (p = 0.97). PBBs and SEMs were only positively associated in people who were older when they were exposed (p = 0.02 vs. p = 0.91). Many subjects had SEMs enriched in biological pathways, particularly in pathways involved with xenobiotic metabolism and endocrine function. Higher number of SEMs was also associated with higher age acceleration (intrinsic: p = 1.70e-3; extrinsic: p = 3.59e-11), indicating that SEMs may be associated with age-related health problems. Finding an association between environmental contaminants and higher SEMs may provide insight into individual differences in response to environmental contaminants, as well as into the biological mechanism behind SEM formation. Furthermore, these results suggest that people may be particularly vulnerable to epigenetic dysregulation from environmental exposures as they age.