Preterm infants, born before 37 weeks of gestation, have a higher mortality rate and are at risk of long-term medical complications. Approximately half of preterm births have no known fetal or maternal risk factors.
Researchers employed an integrative systems biology approach to characterize the molecular effects of genetic and environmental factors on preterm birth. The authors analyzed whole genome sequences from 791 family trios of mother, father, and infant and combined the data with analysis of maternal RNA sequence expression, DNA methylation, and clinical factors and outcomes.
Of these family trios, 270 represented preterm births, 44 of which were very early, arriving before 28 weeks. The analysis revealed 160 genes associated with preterm births, many of which were active in inflammatory pathways. Of these, 72 genes, some of which had been previously associated with preterm birth, appeared to be candidate biomarker genes for very early preterm birth.
Notably, all three genetic datasets implicated the RAB31 and RABJ genes, both members of the RAS oncogene family. The authors note that in addition to identifying candidate genes for preterm birth the integrative analysis approach can serve as a model for uncovering the basis of other multifactorial diseases.