DNA Methylation, Preterm Birth and Blood Pressure in African American Children: The DPREG Study.
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SUBMITTER: Barcelona V
PROVIDER: S-EPMC8060901 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
Publications
DNA Methylation, Preterm Birth and Blood Pressure in African American Children: The DPREG Study.
Barcelona Veronica V Wang Zeyuan Z DeWan Andrew A Sun Yan V YV Taylor Jacquelyn Y JY
Journal of immigrant and minority health 20210422 2
Preterm birth (< 37 weeks) has been associated with high blood pressure (BP) and cardiovascular disease in adulthood. Epigenetic mechanisms may explain how preterm birth influences later BP. In this study, we examined the association between DNA methylation (DNAm), preterm birth and BP in African American children. We recruited 100 children and collected clinical and birth history data. DNA was extracted from saliva and the Illumina EPIC BeadChip was used for epigenetic analyses. Preterm birth w ...[more]
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Project description:BACKGROUND:The causes of many cases of preterm birth (PTB) remain enigmatic. Increased understanding of how epigenetic factors are associated with health outcomes has resulted in studies examining DNA methylation (DNAm) as a contributing factor to PTB. However, few studies on PTB and DNAm have included African American women, the group with the highest rate of PTB. METHODS:The objective of this review was to systematically analyze the existing studies on DNAm and PTB among African American women. RESULTS:Studies ( N = 10) were limited by small sample size, cross-sectional study designs, inconsistent methodologies for epigenomic analysis, and evaluation of different tissue types across studies. African Americans comprised less than half of the sample in 50% of the studies reviewed. Despite these limitations, there is evidence for an association between DNAm patterns and PTB. CONCLUSIONS:Future research on DNAm patterns and PTB should use longitudinal study designs, repeated DNAm testing, and a clinically relevant definition of PTB and should include large samples of high-risk African American women to better understand the mechanisms for PTB in this population.
| S-EPMC5357599 | biostudies-literature
Project description:BackgroundPreterm birth (< 37 weeks' gestation) is a common outcome of pregnancy that has been associated with increased risk of cardiovascular disease for women later in life. Little is known about the physiologic mechanisms underlying this risk. To date, no studies have evaluated if differences in DNA methylation (DNAm) among women who experience preterm birth are short-term or if they persist and are associated with subsequent cardiovascular sequelae or other health disorders. The purpose of this study was to examine long-term epigenetic effects of preterm birth in African American mothers (n = 182) from the InterGEN Study (2014-2019). In this study, we determine if differences in DNAm exist between women who reported a preterm birth in the last 3-5 years compared to those who had full-term births by using two different approaches: epigenome-wide association study (EWAS) and genome-wide co-methylation analyses.ResultsThough no significant CpG sites were identified using the EWAS approach, we did identify significant modules of co-methylation associated with preterm birth. Co-methylation analyses showed correlations with preterm birth in gene ontology and KEGG pathways. Functional annotation analysis revealed enrichment for pathways related to central nervous system and sensory perception. No association was observed between DNAm age and preterm birth, though larger samples are needed to confirm this further.ConclusionsWe identified differentially methylated gene networks associated with preterm birth in African American women 3-5 years after birth, including pathways related to neurogenesis and sensory processing. More research is needed to understand better these associations and replicate them in an independent cohort. Further study should be done in this area to elucidate mechanisms linking preterm birth and later epigenomic changes that may contribute to the development of health disorders and maternal mood and well-being.
| S-EPMC8418749 | biostudies-literature
Project description:BackgroundFew studies have examined the effects of high blood pressure (BP) in pregnancy, preeclampsia, or eclampsia on later BP, and the epigenetics of this phenomenon is similarly poorly understood, especially among African Americans. The purpose of this study was to examine the association between high BP in pregnancy, epigenomics, and later BP in African American women in the InterGEN Study (n = 250).MethodsIn cross-sectional analyses, regression and linear mixed-effects models were employed to examine the effects of high BP in pregnancy on: (a) epigenetic associations (DNA methylation) and (b) BP 3-5 years after birth. The 850K Illumina EPIC BeadChip was used for evaluating epigenome-wide DNA methylation. High BP in pregnancy, preeclampsia, or eclampsia was self-reported by women, and BP was measured 3-5 years after birth, per JNC-7 guidelines. DNA methylation and clinical BP were the main outcomes.ResultsMean age of enrolled women was 31.2 years, 21.8% were smokers, 58% had some college or higher education, 46.6% reported an annual income <$15 000, and 13.6% reported high BP in pregnancy. After adjustment for obesity, smoking, and age, women with a history of high BP in pregnancy had significantly higher BP than those who did not report this complication (5.39 ± 2.4 mm Hg, P = .030). Epigenome-wide analysis revealed no significant sites after multiple testing correction.ConclusionsWe observed a small, but clinically significant, increase in BP in women who reported high BP in pregnancy 3-5 years after that pregnancy. Future studies with larger sample sizes should examine epigenetic contributions to this finding.
| S-EPMC7876779 | biostudies-literature
Project description:Exposure to psychosocial stress and employment of high effort coping strategies have been identified as risk factors that may partially explain the high prevalence of hypertension among African Americans. One biological mechanism through which stress and coping may affect risk of hypertension is via epigenetic modifications (e.g. DNA methylation) in blood pressure-related genes, however this area remains understudied in African Americans. We used data from the ongoing Intergenerational Blood Pressure Study (InterGEN), a longitudinal study designed to investigate factors that contribute to hypertension risk in African American women (n=120) and their young children, to investigate the association between stress overload, problem solving coping, avoidance coping, and social support coping with DNA methylation (DNAm) in 25 candidate genes related to blood pressure. Multivariable linear regression and multilevel modeling were used to conduct methylation site level and gene level analyses respectively. In site level analyses, stress overload, problem solving coping, social support coping, and avoidance coping were associated with 47, 63, 66, and 61 sites respectively at p<0.05. However, no associations were statistically significant after multiple testing correction. There were also no significant associations in gene level analyses. As human social epigenomics is an emerging, evolving area of research there is much to be learned from studies with statistically significant findings as well as studies with null findings. Factors such as characteristics of the social stressor, source of DNA, and synchronization of exposure and outcome are likely important considerations as we move the field forward.
| S-EPMC7213592 | biostudies-literature
Project description:African Americans are at increased risk for spontaneous preterm birth (PTB). Though PTB is heritable, genetic studies have not identified variants that account for its intergenerational risk, prompting the hypothesis that epigenetic factors may also contribute. The objective of this study was to evaluate DNA methylation from maternal leukocytes to identify patterns specific to PTB and its intergenerational risk. DNA from peripheral leukocytes from African American women that delivered preterm (24-34 weeks; N = 16) or at term (39-41 weeks; N = 24) was assessed for DNA methylation using the HumanMethylation450 BeadChip. In maternal samples, 17,829 CpG sites associated with PTB, but no CpG site remained associated after correction for multiple comparisons. Examination of paired maternal-fetal samples identified 5,171 CpG sites in which methylation of maternal samples correlated with methylation of her respective fetus (FDR < 0.05). These correlated sites were enriched for association with PTB in maternal leukocytes. The majority of correlated CpG sites could be attributed to one or more genetic variants. They were also significantly more likely to be in genes involved in metabolic, cardiovascular, and immune pathways, suggesting a role for genetic and environmental contributions to PTB risk and chronic disease. The results of this study may provide insight into the factors underlying intergenerational risk for PTB and its consequences.
| S-EPMC4622997 | biostudies-literature
Project description:IntroductionExperiencing psychosocial stress is associated with poor health outcomes such as hypertension and obesity, which are risk factors for developing cardiovascular disease. African American women experience disproportionate risk for cardiovascular disease including exposure to high levels of psychosocial stress. We hypothesized that psychosocial stress, such as perceived stress overload, may influence epigenetic marks, specifically DNA methylation (DNAm), that contribute to increased risk for cardiovascular disease in African American women.MethodsWe conducted an epigenome-wide study evaluating the relationship of psychosocial stress and DNAm among African American mothers from the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) cohort. Linear mixed effects models were used to explore the epigenome-wide associations with the Stress Overload Scale (SOS), which examines self-reported past-week stress, event load and personal vulnerability.ResultsIn total, n = 228 participants were included in our analysis. After adjusting for known epigenetic confounders, we did not identify any DNAm sites associated with maternal report of stress measured by SOS after controlling for multiple comparisons. Several of the top differentially methylated CpG sites related to SOS score (P < 1 × 10-5), mapped to genes of unknown significance for hypertension or heart disease, namely, PXDNL and C22orf42.ConclusionsThis study provides foundational knowledge for future studies examining epigenetic associations with stress and other psychosocial measures in African Americans, a key area for growth in epigenetics. Future studies including larger sample sizes and replication data are warranted.
| S-EPMC9554129 | biostudies-literature
Project description:BackgroundPreterm birth is considered a multifactorial condition; however, emerging evidence suggests that genetic variation among individuals may have an important role. Prior studies have suggested that single-nucleotide polymorphisms associated with genes related to the immune system, and particularly the maternal inflammatory response, may be associated with an increased risk of preterm delivery.ObjectiveThe objective of the study was to identify single-nucleotide polymorphisms associated with spontaneous preterm birth <37 weeks within a cohort of African-American women.Study designThis is a secondary analysis of a randomized trial that evaluated periodontal disease and preterm birth. Women were enrolled between 6 and 20 weeks' gestation at 3 prenatal care clinics between 2004 and 2007. Maternal DNA samples were collected and analyzed using a custom 1536 single-nucleotide polymorphismgenotyping array designed to assess genes involved in inflammation. Women were included in this study if they self-identified as African American. We excluded women with a multiple gestation or an indicated preterm delivery. We performed allele- and genotype-based analyses to evaluate the association between spontaneous preterm birth and tag single-nucleotide polymorphisms. We used a logistic regression to adjust for prior preterm birth in our genotype-based analysis. In a subgroup analysis, we compared women who delivered at <34 weeks' gestation to women who delivered at term. Within the microarray, we identified ancestry informative markers and compared global ancestry estimates among women who delivered preterm with those who delivered at term.ResultsOf the 833 African-American women in the study with genotype data, 77 women (9.2%) had a spontaneous preterm birth, whereas 756 women delivered at term. In an allele-based analysis, 4 single-nucleotide polymorphisms related to the genes for protein kinase C-α (PRKCA) were associated with increased risk of spontaneous preterm birth <37 weeks, whereas a single single-nucleotide polymorphism related to fms-related tyrosine kinase 1 (FLT1) was associated with spontaneous preterm birth <34 weeks. A genotype-based analysis revealed similar associations between single-nucleotide polymorphisms related to the PRKCA genes and spontaneous premature delivery. Additionally, single-nucleotide polymorphisms related to matrix metalloproteinase-2 (MMP2), tissue inhibitor of matrix metalloproteinase-2 (TIMP2), and interleukin 16 (IL16) genes were associated with spontaneous preterm birth <37 weeks in genotype-based analysis. Genetic variants related to MMP2, matrix metalloproteinase-1 (MMP1), and leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) genes were associated with higher rates of preterm birth <34 weeks. Ancestry estimates were similar between the women who had a spontaneous preterm birth and those who delivered at term.ConclusionWe identified tag single-nucleotide polymorphisms related to 7 genes that are critical to inflammation, extracellular remodeling, and cell signaling that were associated with spontaneous preterm birth in African-American women. Specifically, we found a strong association with the PRKCA gene. Genetic variation in these regions of the genome may be important in the pathogenesis of preterm birth. Our results should be considered in the design of future genomic studies in prematurity.
| S-EPMC4967390 | biostudies-literature
Project description:Background: Asthma is highly heterogeneous and severity evaluation is key to asthma management. DNA methylation (DNAm) contributes to asthma pathogenesis. This study aimed to identify nasal epithelial DNAm differences between severe and non-severe asthmatic children and evaluate the impact of environmental exposures. Methods: Thirty-three non-severe and 22 severe asthmatic African-American children were included in an epigenome-wide association study. Genome-wide nasal epithelial DNAm and gene expression were measured. CpG sites associated with asthma severity and environmental exposures and predictive of severe asthma were identified. DNAm was correlated with gene expression. Enrichment for transcription factor (TF) binding sites or histone modifications surrounding DNAm differences were determined. Results: We identified 816 differentially methylated CpG positions (DMPs) and 10 differentially methylated regions (DMRs) associated with asthma severity. Three DMPs exhibited discriminatory ability for severe asthma. Intriguingly, six DMPs were simultaneously associated with asthma, allergic asthma, total IgE, environmental IgE, and FeNO in an independent cohort of children. 27 DMPs were associated with traffic-related air pollution or secondhand smoke. DNAm at 22 DMPs were altered by diesel particles or allergen in human bronchial epithelial cells. DNAm levels at 39 DMPs were correlated with mRNA expression. Proximal to 816 DMPs, three histone marks and several TFs involved in asthma pathogenesis were enriched. Conclusions: Significant differences in nasal epithelial DNAm were observed between non-severe and severe asthma in African-American children, a subset of which may be useful to predict disease severity. These CpG sites are subject to the influences of environmental exposures and may regulate gene expression.
2022-04-15 | GSE161485 | GEO
Project description:BackgroundAsthma is highly heterogeneous, and severity evaluation is key to asthma management. DNA methylation (DNAm) contributes to asthma pathogenesis. This study aimed to identify nasal epithelial DNAm differences between severe and nonsevere asthmatic children and evaluate the impact of environmental exposures.MethodsThirty-three nonsevere and 22 severe asthmatic African American children were included in an epigenome-wide association study. Genome-wide nasal epithelial DNAm and gene expression were measured. CpG sites associated with asthma severity and environmental exposures and predictive of severe asthma were identified. DNAm was correlated with gene expression. Enrichment for transcription factor (TF) binding sites or histone modifications surrounding DNAm differences were determined.ResultsWe identified 816 differentially methylated CpG positions (DMPs) and 10 differentially methylated regions (DMRs) associated with asthma severity. Three DMPs exhibited discriminatory ability for severe asthma. Intriguingly, six DMPs were simultaneously associated with asthma, allergic asthma, total IgE, environmental IgE, and FeNO in an independent cohort of children. Twenty-seven DMPs were associated with traffic-related air pollution or secondhand smoke. DNAm at 22 DMPs was altered by diesel particles or allergen in human bronchial epithelial cells. DNAm levels at 39 DMPs were correlated with mRNA expression. Proximal to 816 DMPs, three histone marks and several TFs involved in asthma pathogenesis were enriched.ConclusionsSignificant differences in nasal epithelial DNAm were observed between nonsevere and severe asthma in African American children, a subset of which may be useful to predict disease severity. These CpG sites are subjected to the influences of environmental exposures and may regulate gene expression.
| S-EPMC8110596 | biostudies-literature
Project description:Potentially traumatic experiences have been associated with chronic diseases. Epigenetic mechanisms, including DNA methylation (DNAm), have been proposed as an explanation for this association. We examined the association of experiences of trauma with epigenome-wide DNAm among African American mothers (n = 236) and their children aged 3-5 years (n = 232; N = 500), using the Life Events Checklist-5 (LEC) and Traumatic Events Screening Inventory-Parent Report Revised (TESI-PRR). We identified no DNAm sites significantly associated with potentially traumatic experience scores in mothers. One CpG site on the ENOX1 gene was methylome-wide-significant in children (FDR-corrected q-value = 0.05) from the TESI-PRR. This protein-coding gene is associated with mental illness, including unipolar depression, bipolar, and schizophrenia. Future research should further examine the associations between childhood trauma, DNAm, and health outcomes among this understudied and high-risk group. Findings from such longitudinal research may inform clinical and translational approaches to prevent adverse health outcomes associated with epigenetic changes.
| S-EPMC9408935 | biostudies-literature