Sabrina A Gerkowicz1, Sarah W Curtis2, Anna K Knight3, Dawayland O Cobb3, Jessica B Spencer1, Karen N Conneely2, Metrecia L Terrell4, Michele Marcus4,5,6, Alica K Smith7,8. 1. Department of Gynecology and Obstetrics, Division of Reproductive Endocrinology and Infertility, Emory University, Atlanta, GA, USA. 2. Genetics and Molecular Biology Program, Department of Human Genetics, Emory University, Atlanta, GA, 30322, USA. 3. Department of Gynecology and Obstetrics, Emory University, 101 Woodruff Circle NE, Suite 4217, Atlanta, GA, 30322, USA. 4. Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA. 5. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA. 6. Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA. 7. Department of Gynecology and Obstetrics, Emory University, 101 Woodruff Circle NE, Suite 4217, Atlanta, GA, 30322, USA. alicia.smith@emory.edu. 8. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 101 Woodruff Circle NE, Suite 4217, Atlanta, GA, 30322, USA. alicia.smith@emory.edu.
Abstract
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).
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).
Entities:
Keywords:
DNA methylation; Endocrine disrupting compounds; Endometriosis; Epigenetics
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