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Research Project 1

PI: Jerome F. Strauss, III, M.D., Ph.D.

Prematurity associated with singleton pregnancies remains high in the U.S., and well above rates in other developed countries. Moreover, there are significant racial/ethnic disparities in the incidence of premature birth, with African Americans experiencing a disproportionate number of preterm births compared to European Americans. Although the basis for this disparity is most likely multi-factorial, there is increasing evidence that genetic variation and gene-environment interaction contribute to the increased risk of preterm birth in African Americans.  One promising approach to elucidate risk factors for prematurity and targets for therapeutic intervention is to search for genes that are associated or linked to this outcome. The focus of the proposed research is on the genetics of preterm birth. We hypothesize that genetics plays into the prematurity in three different ways: 1) There are alleles that predispose to preterm birth in all populations, probably as a result of gene-environment interactions, and those environmental factors may be more prevalent in African American communities; 2) There are alleles of African ancestry that confer greater risk to African Americans, again probably interacting with environmental factors; and 3) Admixture of European ancestry risk alleles into the African ancestry genome confers risk that disproportionately affects African Americans, possibly again because of environmental interactions. 

Knowledge of genotypes that are strongly associated with preterm birth will have several important consequences.  First, genetic markers could be used to identify subjects prospectively who might benefit from early interventions (e.g., lifestyle change or medical therapy).  Genetic markers predicting prematurity could also facilitate and reduce the cost of prevention clinical trials through identification of high-risk individuals and exclusion of low risk subjects.  Finally, genetic markers could refine understanding of the normal as well as pathologic processes underlying parturition, and lead to innovative medical treatments based on contributing genes.