Summary
This international meta-analysis of 84,689 infants identified a fetal genetic locus on chromosome 2q13 associated with gestational duration, with replication in an additional 9,291 infants. The association is driven by fetal rather than maternal genotype, and functional studies show the lead variant alters binding of the HIC1 transcriptional repressor at genes encoding interleukin-1 family members, which play roles in pro-inflammatory pathways central to parturition. The findings contribute to understanding of the genetic architecture of pregnancy duration and suggest potential mechanisms linking fetal immunity to the timing of labour.
Regional applicability
The study's findings are relevant to UK maternal and neonatal health policy, as gestational duration outside the term window is associated with increased morbidity and mortality. Understanding fetal genetic contributions to pregnancy duration may inform future risk stratification and counselling in UK obstetric practice, though the clinical utility of individual SNP testing remains to be established.
Key measures
Fetal genome-wide association signals; gestational duration (continuous); early preterm birth, preterm birth, and postterm birth (binary outcomes); SNP rs7594852 effect on HIC1 transcriptional repressor binding
Outcomes reported
The study identified a fetal genome-wide association locus on chromosome 2q13 associated with gestational duration and preterm/postterm birth outcomes. Functional experiments characterised how the lead SNP (rs7594852) alters transcriptional regulation at pro-inflammatory genes involved in parturition.
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