Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth.
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ABSTRACT:
SUBMITTER: Hong X
PROVIDER: S-EPMC5472707 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
Publications
Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth.
Hong Xiumei X Hao Ke K Ji Hongkai H Peng Shouneng S Sherwood Ben B Di Narzo Antonio A Tsai Hui-Ju HJ Liu Xin X Burd Irina I Wang Guoying G Ji Yuelong Y Caruso Deanna D Mao Guangyun G Bartell Tami R TR Zhang Zhongyang Z Pearson Colleen C Heffner Linda L Cerda Sandra S Beaty Terri H TH Fallin M Daniele MD Lee-Parritz Aviva A Zuckerman Barry B Weeks Daniel E DE Wang Xiaobin X
Nature communications 20170609
Preterm birth (PTB) contributes significantly to infant mortality and morbidity with lifelong impact. Few robust genetic factors of PTB have been identified. Such 'missing heritability' may be partly due to gene × environment interactions (G × E), which is largely unexplored. Here we conduct genome-wide G × E analyses of PTB in 1,733 African-American women (698 mothers of PTB; 1,035 of term birth) from the Boston Birth Cohort. We show that maternal COL24A1 variants have a significant genome-wide ...[more]
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Project description:IntroductionBMI is a tool to measure maternal nutritional status. Maternal malnutrition is frequently reported health problem especially during child bearing age and effects neonatal birth weight.AimTo determine relationship between prepregnancy maternal BMI and neonatal birth weight.Methods and materialProspective, cross sectional study conducted in Fatima Memorial Hospital, Lahore, Pakistan over a period of 1 year including 2766 mother-neonate pairs. All full term, live born neonates of both gender in early neonatal period (<72 hours) with documented maternal pre-pregnancy and/or first trimester BMI were enrolled. Data analysis using SPSS version 20, was performed.ResultsData analysis of 2766 mother-neonates pairs showed that there were 32.9% overweight and 16.5% obese mothers. More than two third of all overweight and obese mothers were of age group between 26-35 years. Diabetes mellitus, hypertension, medical illness, uterine malformations and caesarean mode of delivery were more prevalent in obese mothers as 22.8%, 10.1%, 13.2%, 2.6% and 75.4% respectively. Mean birth weight, length and OFC increased with increasing maternal BMI. Comparing for normal weight mothers, underweight mothers were at increased risk of low birth weight (p< 0.01) and low risk of macrosomic neonates (p<0.01). However overweight and obese mothers were comparable to normal weight mothers for delivering macrosomic neonates (p 0.89 and p 0.66 respectively).ConclusionsOur study highlights that direct relationship exists between maternal BMI and neonatal birth weight.
| S-EPMC7592734 | biostudies-literature
Project description:BackgroundMaternal pre-pregnancy obesity is an established risk factor for childhood obesity. Investigating epigenetic alterations induced by maternal obesity during fetal development could gain mechanistic insight into the developmental origins of childhood obesity. While obesity disproportionately affects underrepresented racial and ethnic mothers and children in the USA, few studies investigated the role of prenatal epigenetic programming in intergenerational obesity of these high-risk populations.MethodsThis study included 903 mother-child pairs from the Boston Birth Cohort, a predominantly urban, low-income minority birth cohort. Mother-infant dyads were enrolled at birth and the children were followed prospectively to age 18 years. Infinium Methylation EPIC BeadChip was used to measure epigenome-wide methylation level of cord blood. We performed an epigenome-wide association study of maternal pre-pregnancy body mass index (BMI) and cord blood DNA methylation (DNAm). To quantify the degree to which cord blood DNAm mediates the maternal BMI-childhood obesity, we further investigated whether maternal BMI-associated DNAm sites impact birthweight or childhood overweight or obesity (OWO) from age 1 to age 18 and performed corresponding mediation analyses.ResultsThe study sample contained 52.8% maternal pre-pregnancy OWO and 63.2% offspring OWO at age 1-18 years. Maternal BMI was associated with cord blood DNAm at 8 CpG sites (genome-wide false discovery rate [FDR] < 0.05). After accounting for the possible interplay of maternal BMI and smoking, 481 CpG sites were discovered for association with maternal BMI. Among them 123 CpGs were associated with childhood OWO, ranging from 42% decrease to 87% increase in OWO risk for each SD increase in DNAm. A total of 14 identified CpG sites showed a significant mediation effect on the maternal BMI-child OWO association (FDR < 0.05), with mediating proportion ranging from 3.99% to 25.21%. Several of these 14 CpGs were mapped to genes in association with energy balance and metabolism (AKAP7) and adulthood metabolic syndrome (CAMK2B).ConclusionsThis prospective birth cohort study in a high-risk yet understudied US population found that maternal pre-pregnancy OWO significantly altered DNAm in newborn cord blood and provided suggestive evidence of epigenetic involvement in the intergenerational risk of obesity.
| S-EPMC10463574 | biostudies-literature
Project description:BackgroundMaternal stress is potentially a modifiable risk factor for spontaneous preterm birth (sPTB). However, epidemiologic findings on the maternal stress-sPTB relationship have been inconsistent.MethodsTo investigate whether the maternal stress-sPTB associations may be modified by genetic susceptibility, we performed genome-wide gene × stress interaction analyses in 1490 African-American women from the Boston Birth cohort who delivered term (n = 1033) or preterm (n = 457) infants. Genotyping was performed using Illumina HumanOmni 2.5 array. Replication was performed using data from the NICHD genomic and Proteomic Network (GPN) for PTB research.Resultsrs35331017, a T-allele insertion/deletion polymorphism in the protein-tyrosine phosphatase receptor Type D (PTPRD) gene, was the top hit that interacted significantly with maternal lifetime stress on risk of sPTB (PG × E = 4.7 × 10-8). We revealed a dose-responsive association between degree of stress and risk of sPTB in mothers carrying the insertion/insertion genotype, but an inverse association was observed in mothers carrying the heterozygous or deletion/deletion genotypes. This interaction was replicated in African-American (PG × E = 0.088) and Caucasian mothers (PG × E = 0.023) from the GPN study.ConclusionWe demonstrated a significant maternal PTPRD × stress interaction on sPTB risk. This finding, if further confirmed, may provide new insight into individual susceptibility to stress-induced sPTB.ImpactThis was the first preterm study to demonstrate a significant genome-wide gene-stress interaction in African Americans, specifically, PTPRD gene variants can interact with maternal perceived stress to affect risk of spontaneous preterm birth. The PTPRD × maternal stress interaction was demonstrated in African Americans and replicated in both African Americans and Caucasians from the GPN study. Our findings highlight the importance of considering genetic susceptibility in assessing the role of maternal stress on spontaneous preterm birth.
| S-EPMC8400921 | biostudies-literature
Project description:The aims were to investigate the association of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with breastfeeding (BF) duration and BF pattern at 3 months of age.This was a prospective cohort study of 4231 children who were enrolled at birth and were followed-up at 3, 12, 24 and 48 months of age to gather information on maternal and offspring characteristics including BF patterns and BF duration. Maternal pre-pregnancy BMI was categorized according to the WHO classification and GWG according to the 2009 Institute of Medicine recommendations. Cox's proportional hazards model was used to assess whether pre-pregnancy BMI and GWG were associated with BF and exclusive breastfeeding (EBF) duration. Predicted probabilities of BF patterns at 3 months were estimated by multinomial logistic regression.Information on BF was available to 4011 infants. The total BF and EBF median durations were 7.0 months and 1.5 months, respectively. There were no differences in duration of any BF or EBF according to pre-pregnancy BMI or GWG categories. There was an increased predicted probability for weaning before the age of 3 months among infants from obese women, compared with those from mothers with normal pre-pregnancy BMI, with margins adjusted predictions of 0.36 (95% confidence interval (CI) 0.31-0.41) and 0.23 (95% CI 0.21-0.25), respectively.Infants from pre-pregnancy overweight/obese mothers presented higher probability of early weaning compared with infants from normal-weight mothers. Obese/overweight pregnant women need supplementary guidance about BF benefits to infant health during prenatal and postnatal care.
| S-EPMC4827014 | biostudies-other
Project description:Neonatal adiposity has many determinants and may be a risk factor for future obesity. Epigenetic regulation of metabolically important genes is a potential contributor.The objective of the study is to determine whether methylation changes in the LEP gene in cord blood DNA are impacted by the maternal environment or affect neonatal adiposity measures.A cross-sectional study of 114 full-term neonates born to healthy mothers with normal glucose tolerance was performed. Cord blood was assayed for leptin and genome-wide DNA methylation profiles via the Illumina 450K platform. Neonatal body composition was measured by air displacement plethysmography. Multivariate linear regression models and semi-partial correlation coefficients were used to analyze associations. False discovery rate was estimated to account for multiple comparisons.Maternal pre-pregnancy BMI was associated with decreased methylation at five CpG sites near the LEP transcription start site in an adjusted model (false discovery rate <0.022 for each site). The association between maternal BMI and cord blood leptin approached significance (r?=?0.18, p?=?0.054). Cord blood leptin was positively correlated with neonatal adiposity measures including birth weight (r?=?0.45, p?<?0.001), fat mass (r?=?0.47, p?<?0.001) and percent body fat (r?=?0.44, p?<?0.001).Maternal pre-pregnancy BMI is strongly associated with decreased cord blood LEP gene methylation and may mediate the well-known association between maternal pre-pregnancy BMI and neonatal adiposity.
| S-EPMC5462869 | biostudies-literature
Project description:We conducted a genome-wide placental transcriptome study aiming at the identification of functional pathways representing the molecular link between maternal pre-pregnancy BMI and fetal growth. We used RNA microarray (Agilent 8 X 60 K), medical records, and questionnaire data from 183 mother-newborn pairs from the ENVIRONAGE birth cohort study (Flanders, Belgium). We applied a weighted gene co-expression network analysis (WGCNA) and identified genes modules and hub genes that were associated with maternal BMI as well as newborn birth weight. Modules of interest were further characterized by gene ontology (GO) and pathway enrichment analyses. We assessed the mediating effects of modules and hub genes in the association between maternal BMI and newborn weight.
2019-03-16 | GSE128381 | GEO
Project description:BackgroundMother-to-newborn transmission of obesity-associated microbiota may be modified by birth mode (vaginal vs. Cesarean delivery). Prospective data to test this hypothesis are still sparse.ObjectiveTo examine prospective associations of maternal pre-pregnancy BMI and gestational weight gain with the infant gut microbiome by birth-mode strata.Subjects/methodsIn 335 mother-infant pairs in the New Hampshire Birth Cohort, we ascertained data from questionnaires and medical records, and generated microbiome data from 6-week-old infants' stool using Illumina 16s rRNA gene sequencing (V4-V5 region). Analyses were stratified by birth mode and conducted before and after adjusting for potential confounders, which included maternal age, education, parity, and Mediterranean diet score.ResultsAmong 335 mothers, 56% had normal pre-pregnancy BMI ( < 25, referent), 27% were overweight (BMI 25-30), and 18% obese (BMI > 30). Among the 312 mothers with weight gain data, 10% had inadequate weight gain, 30% adequate (referent), and 60% excess. Birth mode modified associations of pre-pregnancy BMI with several genera, including the most abundant genus, Bacteroides (P for interaction = 0.05). In the vaginal-delivery group, maternal overweight or obesity was associated with higher infant gut microbiome diversity and higher relative abundance of 15 operational taxonomic units (OTUs), including overrepresentation of Bacteroides fragilis, Escherichia coli, Veillonella dispar, and OTUs in the genera Staphylococcus and Enterococcus. In the Cesarean-delivered group, there were no significant associations of pre-pregnancy BMI with infant microbiome (alpha) diversity or OTUs. Gestational weight gain was not associated with differential relative abundance of infant gut microbial OTUs or with measures of microbial diversity in infants delivered vaginally or by Cesarean section.ConclusionsAmong vaginally-delivered infants, maternal overweight and obesity was associated with altered infant gut microbiome composition and higher diversity. These associations were not observed in Cesarean-delivered infants, whose microbiome development differs from vaginally-delivered infants. Our study provides additional evidence of birth-mode dependent associations of maternal body weight status with the infant gut microbiota. The role of these associations in mediating the intergenerational cycle of obesity warrants further examination.
| S-EPMC6694002 | biostudies-literature
Project description:Maternal body mass index (BMI) before pregnancy is known to affect both fetal growth and later-life health of the newborn, yet the implicated molecular mechanisms remain largely unknown. As the master regulator of the fetal environment, the placenta is a valuable resource for the investigation of processes involved in the developmental programming of metabolic health. We conducted a genome-wide placental transcriptome study aiming at the identification of functional pathways representing the molecular link between maternal BMI and fetal growth. We used RNA microarray (Agilent 8 × 60 K), medical records, and questionnaire data from 183 mother-newborn pairs from the ENVIRONAGE birth cohort study (Flanders, Belgium). Using a weighted gene co-expression network analysis, we identified 17 correlated gene modules. Three of these modules were associated with both maternal pre-pregnancy BMI and newborn birth weight. A gene cluster enriched for genes involved in immune response and myeloid cell differentiation was positively associated with maternal BMI and negatively with low birth weight. Two other gene modules, upregulated in association with maternal BMI as well as birth weight, were involved in processes related to organ and tissue development, with blood vessel morphogenesis and extracellular matrix structure as top Gene Ontology terms. In line with this, erythrocyte-, angiogenesis-, and extracellular matrix-related genes were among the identified hub genes. The association between maternal BMI and newborn weight was significantly mediated by gene expression for 5 of the hub genes (FZD4, COL15A1, GPR124, COL6A1, and COL1A1). As some of the identified hub genes have been linked to obesity in adults, our observation in placental tissue suggests that biological processes may be affected from prenatal life onwards, thereby identifying new molecular processes linking maternal BMI and fetal metabolic programming.
| S-EPMC6501552 | biostudies-literature
Project description:BackgroundIt is well-established that parental obesity is a strong risk factor for offspring obesity. Further, a converging body of evidence now suggests that maternal weight profiles may affect the developing offspring's brain in a manner that confers future obesity risk. Here, we investigated how pre-pregnancy maternal weight status influences the reward-related striatal areas of the offspring's brain during in utero development.MethodsWe used diffusion tensor imaging to quantify the microstructure of the striatal brain regions of interest in neonates (N = 116 [66 males, 50 females], mean gestational weeks at birth [39.88], SD = 1.14; at scan [43.56], SD = 1.05). Linear regression was used to test the associations between maternal pre-pregnancy body mass index (BMI) and infant striatal mean diffusivity.ResultsHigh maternal pre-pregnancy BMI was associated with higher mean MD values in the infant's left caudate nucleus. Results remained unchanged after the adjustment for covariates.ConclusionsIn utero exposure to maternal adiposity might have a growth-impairing impact on the mean diffusivity of the infant's left caudate nucleus. Considering the involvement of the caudate nucleus in regulating eating behavior and food-related reward processing later in life, this finding calls for further investigations to define the prognostic relevance of early-life caudate nucleus development and weight trajectories of the offspring.
| S-EPMC10964641 | biostudies-literature
Project description:IntroductionHuman anelloviruses, including torque teno virus (TTV) and torque teno mini virus (TTMV), are ubiquitous in the general population and have no known pathogenicity. We investigated the prevalence and viral load of TTV and TTMV in plasma and saliva over pregnancy, and assessed their association with spontaneous or medically indicated preterm birth.MethodsThis is a secondary analysis of the Measurement of Maternal Stress (MOMS) study, which recruited 744 individuals with singleton pregnancies from 4 US sites (Chicago, Pittsburgh, San Antonio, and rural Pennsylvania). Baseline outpatient visits took place in the second trimester (between 12'0 and 20'6/7 weeks' gestation), and follow-up visits in the third trimester (between 32'0 and 35'6/7 weeks' gestation). In a case-control study design, participants who delivered preterm (<37 weeks) resulting from spontaneous labor and/or preterm premature rupture of membranes ("sPTB") were compared with participants experiencing medically indicated preterm birth ("iPTB"), or delivery at term ("controls"). Plasma and saliva samples obtained during the second and third trimesters were tested for the presence and quantity of TTV and TTMV using real-time PCR. Demographic data were obtained via self-report, and clinical data via medical record review by trained research personnel.ResultsTTV was detected in plasma from 81% (second trimester) and 77% (third trimester) of participants, and in saliva from 64 and 60%. Corresponding detection rates for TTMV were 59 and 41% in plasma, and 35 and 24% in saliva. TTV and TTMV concentrations were similar between matched plasma and saliva samples. TTV prevalence and concentrations were not significantly different between groups (sPTB, iPTB, and controls). However, plasma TTMV in the third trimester was associated with sPTB and earlier gestational age at delivery. The iPTB group was not different from either the sPTB or the control group. In saliva, concentrations of TTV and TTMV were similar among the three groups. Both TTV and TTMV were more prevalent with increasing parity and were more common in Black and Hispanic participants compared to non-Hispanic White participants.ConclusionAnellovirus presence (specifically, TTMV) in the third trimester may be associated with preterm birth. Whether this association is causative remains to be determined.
| S-EPMC10309558 | biostudies-literature