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DNA methylation provides insight into intergenerational risk for preterm birth in African Americans.

ABSTRACT: 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.

SUBMITTER: Parets SE

PROVIDER: S-EPMC4622997 | biostudies-literature |

REPOSITORIES: biostudies-literature

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A Systematic Review of DNA Methylation and Preterm Birth in African American Women.

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

DNA Methylation, Preterm Birth and Blood Pressure in African American Children: The DPREG Study.

Project description: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 was not associated with systolic or diastolic BP. No significant DNAm sites were associated with preterm birth in candidate gene methylation analyses. Body mass index was associated with systolic BP (p = 0.01). We did not observe an effect of preterm birth on DNAm or BP in early childhood. Our study is one of the few, however, to examine these associations among African Americans.

| S-EPMC8060901 | biostudies-literature

Admixture mapping to identify spontaneous preterm birth susceptibility loci in African Americans.

Project description:Preterm birth is 1.5 times more common in African American (17.8%) than European American women (11.5%), even after controlling for confounding variables. We hypothesize that genetic factors may account for this disparity and can be identified by admixture mapping.This is a secondary analysis of women with at least one prior spontaneous preterm birth enrolled in a multicenter prospective study. DNA was extracted and whole-genome amplified from stored saliva samples. Self-identified African American patients were genotyped with a 1,509 single nucleotide polymorphism (SNP) commercially available admixture panel. A logarithm of odds locus-genome score of 1.5 or higher was considered suggestive and 2 or higher was considered significant for a disease locus.One hundred seventy-seven African American women with one or more prior spontaneous preterm births were studied. One thousand four hundred fifty SNPs were in Hardy-Weinberg equilibrium and passed quality filters. Individuals had a mean of 78.3% to 87.9% African American ancestry for each SNP. A locus on chromosome 7q21-22 was suggestive of an association with spontaneous preterm birth before 37 weeks of gestation (three SNPs with logarithm of odds scores 1.50-1.99). This signal strengthened when women with at least one preterm birth before 35.0 (eight SNPs with logarithm of odds scores greater than 1.50) and before 32.0 weeks of gestation were considered (15 SNPs with logarithm of odds scores greater than 1.50). No other areas of the genome had logarithm of odds scores higher than 1.5.Spontaneous preterm birth in African American women may be genetically mediated by a susceptibility locus on chromosome 7. This region contains multiple potential candidate genes, including collagen type 1-?-2 gene and genes involved with calcium regulation.

| S-EPMC3094723 | biostudies-literature

DNA methylation changes in African American women with a history of preterm birth from the InterGEN study.

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

Accelerated DNA methylation age and medication use among African Americans.

Project description:DNA methylation age acceleration, the discrepancy between epigenetic age and chronological age, is associated with mortality and chronic diseases, including diabetes, hypertension, and hyperlipidemia. In this study, we investigate whether medications commonly used to treat these diseases in 15 drug categories are associated with four epigenetic age acceleration measures: HorvathAge acceleration (HorvathAA), HannumAge acceleration (HannumAA), PhenoAge acceleration, and GrimAge acceleration (GrimAA) using cross-sectional (Phase 1, N=1,100) and longitudinal (Phases 1 and 2, N=266) data from African Americans in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. In cross-sectional analyses, the use of calcium channel blockers was associated with 1.27 years lower HannumAA after adjusting for covariates including hypertension (p=0.001). Longitudinal analyses showed that, compared to those who never used antihypertensives, those who started to take antihypertensives after Phase 1 had a 0.97-year decrease in GrimAA (p=0.007). In addition, compared to those who never used NSAID analgesics, those who started to take them after Phase 1 had a 2.61-year increase in HorvathAA (p=0.0005). Our study demonstrates that three commonly used medications are associated with DNAm age acceleration in African Americans and sheds light on the potential epigenetic effects of pharmaceuticals on aging at the cellular level.

| S-EPMC8221348 | biostudies-literature

Spontaneous preterm birth in African Americans is associated with infection and inflammatory response gene variants.

Project description:The objective of the study was to study the genetic risk factors of spontaneous preterm birth (PTB) in African Americans.Case-control analyses were performed using maternal and fetal deoxyribonucleic acid from 279 African American birth events (82 PTB and 197 term) and 1432 single-nucleotide polymorphisms from 130 candidate genes. Single-locus association and haplotype analyses were performed.The most significant associations were in the maternal interleukin (IL)-15 (rs10833, allele P = 2.91 x 10(-4), genotype P = 2.00 x 10(-3)) gene and the fetal IL-2 receptor B (IL-2RB) (rs84460, allele P = 1.37 x 10(-4), genotype P = 6.29 x 10(-4)) gene. The best models for these markers were additive (rs10833, odds ratio [OR], 0.30; 95% confidence interval [CI], 0.14-0.62; P = 1.0 x 10(-3); rs84460, OR, 2.32; 95% CI, 1.47-3.67; P < 1.0 x 10(-3)). The largest number of significant associations was found in genes related to infection and inflammation. There were overall a larger number of significant associations in infants than in mothers.These results support a strong role for genes involved in infection and inflammation in the pathogenesis of PTB, particularly IL-12 and IL-12RB, and indicate that in African Americans there may be complementarity of maternal and fetal genetic risks for PTB.

| S-EPMC4829203 | biostudies-literature

DNA Methylation of African Americans from the Grady Trauma Project

2015-09-03 | GSE72680 | GEO

DNA Methylation of African Americans from the Grady Trauma Project

Project description:Childhood and cumulative exposure to trauma increases an individual's lifetime risk for psychiatric and stress-related disorders. This study evaluates DNA methylation in whole blood from African American participants, with the goal of identifying associaitons between peripheral DNA methylation and psychiatric symptoms. DNA methylation was assessed in whole blood from participants of the Grady Trauma Project. Blood was collected in EDTA vacuum tubes prior to extraction. DNA methylation was interrogated for each sample using the HumanMethylation450 BeadChip (Illumina).

2015-09-03 | E-GEOD-72680 | biostudies-arrayexpress

Novel DNA methylation sites associated with cigarette smoking among African Americans.

Project description:IntroductionCigarette smoking has been associated with adverse health outcomes for mothers and children and is a major contributor to heart disease. Although cigarette smoking is known to affect the epigenome, few studies have been done in African American populations. In this study, we investigated the association between cigarette smoking and DNA methylation (DNAm) among African Americans from the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure Study (InterGEN), and the Genetic Epidemiology Network of Arteriopathy (GENOA).MethodsThe InterGEN study aims to examine the effects of genetic and psychological factors on blood pressure among African American women and their children. Current cigarette smoking was assessed at baseline. DNAm of saliva was assessed using the 850K EPIC Illumina BeadChip for Epigenome-Wide Association analyses. A replication study was conducted among 1100 participants in the GENOA study using the same BeadChip.ResultsAfter controlling for age, body mass index, population structure and cell composition, 26 epigenome-wide significant sites (FDR q < 0.05) were identified, including the AHRR and PHF14 genes associated with atherosclerosis and lung disease, respectively. Six novel CpG sites were discovered in the InterGEN sample and replicated in the GENOA sample. Genes mapped include RARA, FSIP1, ALPP, PIK3R5, KIAA0087, and MGAT3, which were largely associated with cancer development.ConclusionWe observed significant epigenetic associations between smoking and disease-associated genes (e.g., cardiovascular disease, lung cancer). Six novel CpG sites were identified and replicated across saliva and blood samples.

| S-EPMC6557550 | biostudies-literature

Epigenomic association analysis identifies smoking-related DNA methylation sites in African Americans.

Project description:Cigarette smoking is an environmental risk factor for many chronic diseases, and disease risk can often be managed by smoking control. Smoking can induce cellular and molecular changes, including epigenetic modification, but the short- and long-term epigenetic modifications caused by cigarette smoking at the gene level have not been well understood. Recent studies have identified smoking-related DNA methylation (DNAm) sites in Caucasians. To determine whether the same DNAm sites associate with smoking in African Americans, and to identify novel smoking-related DNAm sites, we conducted a methylome-wide association study of cigarette smoking using a discovery sample of 972 African Americans, and a replication sample of 239 African Americans with two array-based methods. Among 15 DNAm sites significantly associated with smoking after correction for multiple testing in our discovery sample, 5 DNAm sites are replicated in an independent cohort, and 14 sites in the replication sample have effects in the same direction as in the discovery sample. The top two smoking-related DNAm sites in F2RL3 (factor II receptor-like 3) and GPR15 (G-protein-coupled receptor 15) observed in African Americans are consistent with previous findings in Caucasians. The associations between the replicated DNAm sites and smoking remain significant after adjusting for genetic background. Despite the distinct genetic background between African Americans and Caucasians, the DNAm from the two ethnic groups shares common associations with cigarette smoking, which suggests a common molecular mechanism of epigenetic modification influenced by environmental exposure.

| S-EPMC3744600 | biostudies-literature

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