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Study Description

Preterm delivery resulting in the birth of a premature infant is a complex problem with a devastating impact on individuals, families and society. The prevalence of preterm birth has increased steadily in developed countries over the last 20 years and more than three million children die of preterm birth worldwide each year. Despite the importance of the problem and its disproportionate occurrence in poor and minority populations, the underlying causes have been difficult to identify. Spontaneous preterm labor has as its suspected triggers infection, stress, poor nutrition and inherited factors. The single best predictor for preterm delivery is a previous preterm birth. Studies of twins and of recurrences within families provide evidence that genetic factors underlie a substantive component of the risk for prematurity. One major challenge in studying genetic factors in prematurity is that the risk case is not truly established. The genetic risk could reside either in the mother and her uterus or in the infant/placenta. Identification of genetic factors in the mother and/or infant could provide insights into identifying relevant environmental covariates that may be more amenable to rapid interventions but difficult to find using standard epidemiology alone. A comprehensive genome-wide association study (GWAS) is the ideal way to identify those genes that would not be suspected based on our current understanding of the biology of parturition. We are using 2200 African American samples with term or preterm labor. A subset of these (~800) are infant samples recruited by the Neonatal Research Network as part of a study on cytokines and infection in extremely low birth weight infants (Schelonka RL, et al., 2011. PMID: 21145756). Therefore, this group consists of infants <1,000 grams with clinical outcome data for the infant allowing study of the genetic contributors for not only preterm birth but also the complications that often accompany preterm birth. The result will enable a better understanding of the biology of parturition and suggest environmental modifications that can prolong gestations to improve neonatal and adult outcomes.

This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to preterm birth through large-scale genome-wide association studies of African-American cases and controls from multiple sites in the United States. 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.

  • Study Type: Case-Control
  • Number of study subjects that have individual level data available through Authorized Access: 3478

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

In the course of routine data cleaning and data analyses, investigators may incidentally identify genetic abnormalities that might influence the clinical care of an individual. These statements and recommendations have been developed to help investigators when they are informed of any such incidental findings.

  1. GENEVA Statement on Incidental Findings
  2. GENEVA Aneuploidy Reference Table
  3. GENEVA Pharmacogenetic Variants Reference Table

Study Inclusion/Exclusion Criteria

This study is comprised of six "primary sites". All samples from site 1 are premature case (23-29 gestational weeks) infants with maternal self report of African-American regarding the child's race. Samples from site 2 include African-American case (23-36 weeks) and control (37-41 weeks) mothers and infants. Infants were classified as African-American based on maternal self-reported race only. Samples from site 3 include African-American infant and mother cases (24-36 weeks). Infant race was defined as African-American if either parent self-reported African-American ancestry. Samples from site 4 include infant and mother cases (22-36 weeks) and controls (37-41 weeks). African-American race for the infant was determined if both maternal and paternal individuals self identified as African-American and Non-Hispanic ethnicity. Additionally, both maternal and paternal parents and grandparents also had to be self-identified Non-Hispanic African-Americans. Samples from site 5 include African-American infant and mother cases (23-36 weeks) and infant controls (37-42 weeks). Infants were classified as African-American based on maternal self-reported race only. All samples from site 6 are case (20-33 weeks) infants. For site 6, the project was a retrospective use of blood spot filter cards that had been collected as part of the study of infection and cytokines in very low birth weight (less than 1000 grams) neonates where a substantial portion of the populations were African-American.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Genotyping Illumina HumanOmni1-Quad_v1-0_B 1051295 1049033
Study History

Although the central theme of the overall design was to collect case-parent trios, the aggregate group had a mixture of mother-baby pairs, isolated cases and isolated controls. Most subjects were recruited as part of ongoing studies of preterm birth either through the Neonatal Intensive Care Unit (NICU) or by obstetrician's referral. This study is comprised of six "primary sites." All samples from sites 1, 2, 4 and 5 were recruited from a single hospital; while samples from site 3 were recruited from four different sites around the U.S. and samples from site 6 were recruited from 12 different hospitals.

Selected publications
Diseases Related to Study (MESH terms)
Links to Other NCBI Resources
Authorized Data Access Requests
Study Attribution
  • Principal Investigator
    • Jeffrey C. Murray. Department of Pediatrics, University of Iowa, Iowa City, IA, USA
  • Funding Source
    • R01 HD057192-01A2. National Institutes of Health, Bethesda, MD, USA
    • R01 HD052953-01. National Institutes of Health, Bethesda, MD, USA
  • Genotyping Center
    • Johns Hopkins University Center for Inherited Disease Research (CIDR), Baltimore, MD, USA
  • Funding Source for Genotyping
    • U01HG004438-01. NIH GEI grant "JH/CIDR Genotyping for Genome-Wide Association Studies". National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA