Nulliparity modifies the maternal genetic effects on gestational duration but not on birth weight

Gestational duration and birth weight are linked to adverse health outcomes in offspring and mothers. Previous genome-wide association studies (GWAS) on these pregnancy outcomes did not consider parity, despite its known effects on mean values and variance. Here, we explored whether nulliparity (no previous births) modified the maternal or fetal genetic effects on gestational duration and birth weight, and resolved effect origin in up to 58,528 mothers and fetuses from the Norwegian Mother, Father, and Child Cohort Study. We identified shared and distinct loci for each outcome in parity-stratified GWAS. For gestational duration, we identified more maternal loci in nulliparous women, and a polygenic predictor had a three-fold higher prediction accuracy among nulliparous compared to multiparous women (p-value interaction = 5x10-5), with validation in an independent cohort. The results for birth weight showed discrepancies between the number of loci and the polygenic predictor. Our study reveals that nulliparity modifies the maternal genetic effects on gestational duration and highlights the relevance of considering nulliparity in genetic, and likely experimental, studies on pregnancy outcomes. TeaserGenome-wide study highlights that maternal genetics affect pregnancy length more strongly in first pregnancy.