Born too soon  pg. 5

Now at Vanderbilt, Muglia’s team is one of many searching for genes that will predict whether a woman has an increased risk of having a preterm infant.

For the past several years, investigators including Scott Williams, Ph.D., an investigator in the Vanderbilt Center for Human Genetics Research, have assessed variations in so-called “candidate genes” – genes with roles in biological pathways that are hypothesized to increase risk for preterm birth (such as infection- and inflammation-related pathways).

 
Scott Williams, Ph.D.
Photo by Susan Urmy
 
 

And although they have found compelling associations for certain genes and preterm birth in some study groups, corroborating these findings in other groups of women has been difficult.

“One of the problems with the genetic studies to date is that preterm birth clearly falls into multiple, heterogeneous sub-phenotypes,” Williams points out.

Sub-grouping preterm births based on characteristics such as preterm rupture of membranes, presence of infection or week of gestation (early, mid or late preterm), he says, might improve investigators’ ability to find genetic culprits. But such sub-grouping comes at a cost in numbers, and genetic studies rely on very large groups of patients in order to have the statistical power to find small but biologically important differences.

As a next step in the gene chase, the field is banding together to conduct “genome wide association studies” (GWAS) – analyses that search for common genetic variation that increases susceptibility for preterm birth. Common genetic variants are spots in the genome where a variable “letter” of the DNA code is present in at least 5 percent of the population. Williams is one of the leaders of an international consortium (the Preterm Birth Genome Project) that is contributing DNA samples to a combined dataset for analysis.

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