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

Pol Solé-Navais; Christopher J. Flatley; Valgerður Steinthórsdóttir; Marc Vaudel; Julius Juodakis; Jing Chen; Triin Laisk; Abigail Leavitt LaBella; David Westergaard; Jonas Bačelis; Ben Michael Brumpton; Line Skotte; Maria Carolina Borges; Øyvind Helgeland; Anubha Mahajan; Matthias Wielscher; Frederick T. J. Lin; Catherine Briggs; Carol A. Wang; Gunn-Helen Moen; Robin N. Beaumont; Jonathan P. Bradfield; Abin Abraham; Guðmar Þorleifsson; Maiken Elvestad Gabrielsen; Sisse Rye Ostrowski; Dominika Modzelewska; Ellen Aagaard Nohr; Elina Hyppönen; Amit Kumar Srivastava

doi:10.1038/s41588-023-01343-9

Genetic & Genomic MedicineNature GeneticsApr 1, 2023

Peer-reviewed journal article

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

Pol Solé-Navais iD, Christopher J. Flatley iD, Valgerður Steinthórsdóttir iD, Marc Vaudel iD, Julius Juodakis iD, Jing Chen iD, Triin Laisk iD, Abigail Leavitt LaBella iD, David Westergaard iD, Jonas Bačelis iD, Ben Michael Brumpton iD, Line Skotte iD, Maria Carolina Borges iD, Øyvind Helgeland iD, Anubha Mahajan iD, Matthias Wielscher iD, Frederick T. J. Lin iD, Catherine Briggs, Carol A. Wang iD, Gunn-Helen Moen iD, Robin N. Beaumont iD, Jonathan P. Bradfield, Abin Abraham iD, Guðmar Þorleifsson iD, Maiken Elvestad Gabrielsen iD, , Bo Jacobsson iD

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.

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