Structural and genomic variation in preterm birth

Runs of homozygosity (ROH) are consecutive homozygous genotypes, which may result from population inbreeding or consanguineous marriages. ROH enhance the expression of recessive traits.

We mapped ROH in a case control study of women delivering at term compared with women delivering at or before 34 wk gestation. Gene sets known to be important in risk of preterm birth were examined for their overlap with identified ROH segments.

While we found no evidence of increased burden of ROH or copy number variations in mothers delivering at or before 34 wk compared with term, we identified 424 genome-wide 50 kb segments with significant difference in abundance of overlapping ROH segments in cases vs. controls, P < 0.05. These regions overlap 199 known genes. We found preterm birth associated genes (CXCR4, MYLK, PAK1) and genes shown to have an evolutionary link to preterm (CXCR4, PPP3CB, C6orf57, DUSP13, and SLC25A45) with significant differences in abundance of overlapping ROH blocks in cases vs. controls, P < 0.001.

We conclude, while we found no significant burden of ROH, we did identify genomic regions with significantly greater abundance of ROH blocks in women delivering preterm that overlapped genes known to be involved in preterm birth.