Dataset Information

Genome-Wide Association Study of Preterm Birth

ABSTRACT:

Preterm birth (PTB, born before 37 weeks of gestation) accounts for 12.5% of all births in the U.S. It is a leading cause of neonatal mortality and post-natal morbidity. The highest rate of PTB occurs among the black population (17.8%). Available literature and our research findings strongly suggest that genetic factors play an important role in PTB. Supported by a grant from the NICHD, the goal of this project is to conduct a genome-wide association (GWA) study and apply advanced statistical methods to identify susceptibility loci of PTB. We will genotype 1,000 black mothers who delivered preterm births (cases) and 1,000 age-matched black mothers who delivered term births (controls) at the Boston Medical Center (BMC), using the Illumina HumanOmni 2.5 array. Subsequently, we will perform replication analysis of the SNPs using independent, multi-ethnic samples from the BMC. We also will genotype the significant single-nucleotide polymorphisms (SNPs) in babies born to the study mothers, and examine if the fetal gene interacts with the maternal gene to affect the risk of PTB.

PUBLIC HEALTH REVELANCE: We anticipate that this study will lead to the identification of novel genetic loci of PTB. Such findings not only will provide important insights into mechanisms leading to PTB, but also may help identify women at high-risk of PTB, which in turn, may lead to the development of early and targeted interventions that can prevent PTB or mitigate the severity and consequences of PTB.

PROVIDER: phs000332.v1.p1 | EGA |

REPOSITORIES: EGA

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Publications

Placental inflammatory response is associated with poor neonatal growth: preterm birth cohort study.

Mestan Karen K Yu Yunxian Y Matoba Nana N Cerda Sandra S Demmin Bethany B Pearson Colleen C Ortiz Katherin K Wang Xiaobin X

Pediatrics 20100322 4

<h4>Objective</h4>We sought to determine whether placental markers of intrauterine inflammation were associated with poor weight gain among premature infants in the neonatal period.<h4>Methods</h4>We reviewed 697 preterm births prospectively enrolled as part of an ongoing molecular epidemiological study. Placental markers and serial weight gain were analyzed for premature infants who were hospitalized for >/=21 days (N = 256). Placentas were examined for maternal inflammatory response (MIR), def ...[more]

PMID: 20308216

Publication: 1/11

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Project description:<p>Preterm birth (PTB, born before 37 weeks of gestation) is a leading cause of neonatal mortality and post-natal morbidity. PTB affects one in nine all live births in the U.S. Notably, the highest rate of PTB occurs among African Americans (one in six). PTB is a complex trait, likely determined by multiple environmental and genetic factors and their interactions. We demonstrated strong familial aggregation of preterm and low birthweight in the US Blacks and Whites (Wang et al, NEJM, <a href="http://www.ncbi.nlm.nih.gov/pubmed/7491139">1995</a>) and conducted the largest candidate gene study of preterm birth at that time (Hao et al, HMG, <a href="http://www.ncbi.nlm.nih.gov/pubmed?cmd=DetailsSearch&term=14976157">2004</a>). We showed that a subset of mothers with certain metabolic gene variants are particularly vulnerable to the adverse effects of cigarette smoking on low birthweight and preterm births (Wang et al, JAMA, <a href="http://www.ncbi.nlm.nih.gov/pubmed?cmd=DetailsSearch&term=11779261">2002</a>). We also published a number of papers that examined the effect of maternal pre-pregnancy BMI, micronutrient status, stress and environmental toxins on the risk of preterm birth and related conditions.</p> <p>This project, supported by a grant from the NICHD (2R01HD41702, PI, Xiaobin Wang), aimed to conduct a genome-wide association study (GWAS) and apply advanced statistical methods to identify susceptibility loci of PTB in a predominantly urban low-income African American sample, a subset of the Boston Birth Cohort.</p> <p>PUBLIC HEALTH REVELANCE: We anticipate that this study will lead to the identification of novel genetic loci of PTB and gene-environment interactions. Such findings not only will provide important insights into mechanisms leading to PTB, but also may help identify women at high-risk of PTB, which in turn, may lead to the development of early and targeted interventions that can prevent PTB or mitigate the severity and consequences of PTB.</p>

Project description:<p>Preterm labor resulting in the delivery of a premature child is a complex problem with an enormous impact on individuals, families and society. An estimated 500,000 children are born prematurely in the U.S. each year, and 5 million worldwide die annually of prematurity and its complications. Prematurity is also the single largest contributor to disability-adjusted life years, a measure of the lifetime impact of a disease. Despite the importance of the problem and its disproportionate occurrence in poor and minority populations, its underlying etiology (or etiologies) remains unknown; the single best predictor for preterm delivery is a previous preterm birth. The largest single cause of prematurity is spontaneous preterm labor, and suspected triggers for this include infection, stress, poor nutrition and genetic factors. Family and twin studies provide strong evidence that genetic factors underlie about 40% of the risk for prematurity. A major challenge in studying genetic factors in prematurity is maternal/uterine factors, fetal/placental factors, or both may influence risk. Thus, any approach to studying preterm birth should account for both infant and maternal risk, environmental covariates and interactions. The Danish National Birth Cohort (DNBC) is a well-established, prospective cohort that enrolled women early in pregnancy, prior to any adverse pregnancy outcomes, to minimize bias in data collection and sampling. See details at: <a href="http://www.ssi.dk/English" target="_blank">http://www.ssi.dk/English</a>.</p> <p>The DNBC followed over 100,000 pregnancies beginning in the first trimester and has extensive biological material and epidemiologic data on health outcomes in both mother and child. The current study posted on dbGaP contains data from a genome-wide case/control study using approximately 1,000 preterm mother-child pairs from the DNBC most with spontaneous onset of labor or preterm premature rupture of membranes (PPROM), along with 1,000 control pairs where the child was born at ~40 weeks' gestation. After data cleaning some small changes in case/control status and other variables resulted in minor changes in numbers of cases or controls in certain categories. Environmental variables are being used as covariates in the analysis.</p> <p>To replicate positive findings, we are using additional mother-child pairs from the DNBC and from the general Danish population, as well as 2200 samples coming primarily from an African-American population known to have high rates of preterm labor and delivery. This group includes over 1000 mostly very low birthweight infants, over 500 infant term controls, 326 term mother/baby pairs and 180 preterm mother/baby pairs. The data from these additional cohorts will be available in separate dbGaP postings. The study is expected to yield a better understanding of the biology of parturition, identify common genetic factors that play a role in preterm birth and its complications and suggest environmental modifications that can prolong gestation, with the goal of improving both neonatal and adult outcomes.</p> <p>This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to prematurity and its complications through large-scale genome-wide association studies of a well-characterized cohort of Danish mothers and babies. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.</p>

Dataset Information

Genome-Wide Association Study of Preterm Birth

Publications

Placental inflammatory response is associated with poor neonatal growth: preterm birth cohort study.

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