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

Tracy A. Manuck, Yinglei Lai, Paul J. Meis, Baha Sibai, Catherine Y. Spong, Dwight J. Rouse, Jay D. Iams, Steve N. Caritis, Mary J. O'sullivan, Ronald J. Wapner, Brian Mercer, Susan M. Ramin, Alan M. Peaceman

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Objective: 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. Methods: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. Rssults: 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. CONCLUSION:: 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-α-2 gene and genes involved with calcium regulation.

Original languageEnglish (US)
Pages (from-to)1078-1084
Number of pages7
JournalObstetrics and gynecology
Volume117
Issue number5
DOIs
StatePublished - May 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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    Manuck, T. A., Lai, Y., Meis, P. J., Sibai, B., Spong, C. Y., Rouse, D. J., Iams, J. D., Caritis, S. N., O'sullivan, M. J., Wapner, R. J., Mercer, B., Ramin, S. M., & Peaceman, A. M. (2011). Admixture mapping to identify spontaneous preterm birth susceptibility loci in African Americans. Obstetrics and gynecology, 117(5), 1078-1084. https://doi.org/10.1097/AOG.0b013e318214e67f