Genetic effects on the timing of parturition and links to fetal birth weight

Abstract

The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (cases = 18,797, controls = 260,246) revealed 6 associated loci, and large genetic similarities with gestational duration. Analysis of the parental transmitted and non-transmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, while seven act both through the maternal and fetal, and two act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight.