Dataset Information

Targeted Sequencing and Meta-Analysis of Preterm Birth.

ABSTRACT: Understanding the genetic contribution(s) to the risk of preterm birth may lead to the development of interventions for treatment, prediction and prevention. Twin studies suggest heritability of preterm birth is 36-40%. Large epidemiological analyses support a primary maternal origin for recurrence of preterm birth, with little effect of paternal or fetal genetic factors. We exploited an "extreme phenotype" of preterm birth to leverage the likelihood of genetic discovery. We compared variants identified by targeted sequencing of women with 2-3 generations of preterm birth with term controls without history of preterm birth. We used a meta-genomic, bi-clustering algorithm to identify gene sets coordinately associated with preterm birth. We identified 33 genes including 217 variants from 5 modules that were significantly different between cases and controls. The most frequently identified and connected genes in the exome library were IGF1, ATM and IQGAP2. Likewise, SOS1, RAF1 and AKT3 were most frequent in the haplotype library. Additionally, SERPINB8, AZU1 and WASF3 showed significant differences in abundance of variants in the univariate comparison of cases and controls. The biological processes impacted by these gene sets included: cell motility, migration and locomotion; response to glucocorticoid stimulus; signal transduction; metabolic regulation and control of apoptosis.

SUBMITTER: Uzun A

PROVIDER: S-EPMC4862658 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Targeted Sequencing and Meta-Analysis of Preterm Birth.

Uzun Alper A Schuster Jessica J McGonnigal Bethany B Schorl Christoph C Dewan Andrew A Padbury James J

PloS one 20160510 5

Understanding the genetic contribution(s) to the risk of preterm birth may lead to the development of interventions for treatment, prediction and prevention. Twin studies suggest heritability of preterm birth is 36-40%. Large epidemiological analyses support a primary maternal origin for recurrence of preterm birth, with little effect of paternal or fetal genetic factors. We exploited an "extreme phenotype" of preterm birth to leverage the likelihood of genetic discovery. We compared variants id ...[more]

PMID: 27163930

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Project description:The results from epidemiologic studies linking blood folate concentrations, folic acid supplementation, or dietary folate to the risk of preterm birth are inconsistent. In this study, we aimed to summarize the available evidence on these associations. A systematic search of the PubMed/MEDLINE, Google Scholar, Web of Science, and Cochrane Library databases up to October 20, 2018 was performed and reference lists of retrieved articles were screened. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the highest vs. the lowest levels of folate concentrations, folic acid supplementation, and dietary folate were calculated using random-effects models. Subgroup analyses and univariate meta-regression were performed to explore the sources of heterogeneity. Ten studies (six prospective cohort studies and four case-control studies) were included on folate concentrations, 13 cohort studies were included about folic acid supplementation, and 4 cohort studies were included regarding dietary folate intake. Higher maternal folate levels were associated with a 28% reduction in the risk of preterm birth (OR 0.72, 95% CI 0.56-0.93). Higher folic acid supplementation was associated with 10% lower risk of preterm birth (OR 0.90, 95% CI 0.85-0.95). In addition, a significant negative association was observed between dietary folate intake and the risk of preterm birth (OR 0.68, 95% CI 0.55-0.84), but no significant relation was seen between dietary folate and the risk of spontaneous preterm birth (OR 0.89, 95% CI 0.57-1.41). In the subgroup analysis, higher maternal folate levels in the third trimester were associated with a lower risk of preterm birth (OR 0.58, 95% CI 0.36-0.94). To initiate taking folic acid supplementation early before conception was adversely associated with preterm birth risk (OR 0.89, 95% CI 0.83-0.95). In conclusion, higher maternal folate levels and folic acid supplementation were significantly associated with a lower risk of preterm birth. The limited data currently available suggest that dietary folate is associated with a significantly decreased risk of preterm birth.

Project description:BackgroundGlobally, complications of preterm birth are among the most common cause of neonatal mortality. In Ethiopia, the neonatal mortality reduction is not worthy of attention. Hence, this study reviewed the prevalence of preterm birth and factors associated with preterm birth in Ethiopia.MethodsThe review protocol of this study has been registered in PROSPERO (CRD42017077356). The PRISMA guideline was followed for this review. Studies that assessed the prevalence and/or associated factors of preterm birth in Ethiopia and published from Jan 01, 2009 to Dec 31, 2019 were considered. Studies were searched from the PubMed and Science Direct among medical electronic databases and Google Scholar. Random-effects model was used for detected heterogeneity among studies. Publication bias and sensitivity analysis were assessed. Pooled estimates with its 95% confidence interval were reported using forest plots. The quality of evidence from the review was assessed using GRADE approach.ResultsTwenty-two studies involving a total of 12,279 participants were included. The overall pooled prevalence of preterm birth in Ethiopia was 10.48% (95% CI: 7.98-12.99). Pooled odds ratio showed rural residence (AOR = 2.34, 95% CI: 1.35-4.05), being anemic (AOR = 2.59, 95% CI: 1.85-3.64), < 4 antenatal care visits (AOR = 2.34, 95%CI: 1.73-3.33), pregnancy induced hypertension (AOR = 3.49, 95% CI: 2.45-4.97), prelabor rapture of membrane (AOR = 4.42, 95% CI: 2.28-8.57), antepartum hemorrhage (AOR = 5.02, 95% CI: 2.90-8.68), multiple pregnancies (AOR = 3.89, 95% CI: 2.52-5.99), past adverse birth outcomes (AOR = 3.24, 95% CI: 2.53-4.15) and chronic illness (AOR = 4.89, 95%CI: 3.12-7.66) were associated with increased likelihood of preterm birth. Further, support during pregnancy was associated with reduced occurrence of preterm birth.ConclusionThe pooled national level prevalence of preterm birth in Ethiopia is high. Socio demographic, nutritional, health care, obstetric and gynecologic, chronic illness and medical conditions, behavioral and lifestyle factors are the major associated factors of preterm birth in Ethiopia. This evidence is graded as low grade. Thus, efforts should be intensified to address reported risk factors to relieve the burden of preterm birth in the study setting, Ethiopia.

Project description:BACKGROUND: Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth. METHODS AND FINDINGS: Two reviewers independently searched seven online databases for contemporaneous (1 January 1995-23 September 2013) epidemiological studies investigating the association between preterm birth and asthma/wheezing disorders. Additional studies were identified through reference and citation searches, and contacting international experts. Quality appraisal was undertaken using the Effective Public Health Practice Project instrument. We pooled unadjusted and adjusted effect estimates using random-effects meta-analysis, investigated "dose-response" associations, and undertook subgroup, sensitivity, and meta-regression analyses to assess the robustness of associations. We identified 42 eligible studies from six continents. Twelve were excluded for population overlap, leaving 30 unique studies involving 1,543,639 children. Preterm birth was associated with an increased risk of wheezing disorders in unadjusted (13.7% versus 8.3%; odds ratio [OR] 1.71, 95% CI 1.57-1.87; 26 studies including 1,500,916 children) and adjusted analyses (OR 1.46, 95% CI 1.29-1.65; 17 studies including 874,710 children). The risk was particularly high among children born very preterm (<32 wk gestation; unadjusted: OR 3.00, 95% CI 2.61-3.44; adjusted: OR 2.81, 95% CI 2.55-3.12). Findings were most pronounced for studies with low risk of bias and were consistent across sensitivity analyses. The estimated population-attributable risk of preterm birth for childhood wheezing disorders was ?3.1%. Key limitations related to the paucity of data from low- and middle-income countries, and risk of residual confounding. CONCLUSIONS: There is compelling evidence that preterm birth-particularly very preterm birth-increases the risk of asthma. Given the projected global increases in children surviving preterm births, research now needs to focus on understanding underlying mechanisms, and then to translate these insights into the development of preventive interventions. REVIEW REGISTRATION: PROSPERO CRD42013004965.

Dataset Information

Targeted Sequencing and Meta-Analysis of Preterm Birth.

Publications

Targeted Sequencing and Meta-Analysis of Preterm Birth.

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