Genetic effects on the timing of parturition and links to fetal birth weight
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Published:2023-04
Issue:4
Volume:55
Page:559-567
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ISSN:1061-4036
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Container-title:Nature Genetics
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language:en
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Short-container-title:Nat Genet
Author:
Solé-Navais PolORCID, Flatley Christopher, Steinthorsdottir ValgerdurORCID, Vaudel MarcORCID, Juodakis JuliusORCID, Chen JingORCID, Laisk TriinORCID, LaBella Abigail L.ORCID, Westergaard DavidORCID, Bacelis JonasORCID, Brumpton BenORCID, Skotte LineORCID, Borges Maria C., Helgeland ØyvindORCID, Mahajan AnubhaORCID, Wielscher MatthiasORCID, Lin FrederickORCID, Briggs Catherine, Wang Carol A.ORCID, Moen Gunn-HelenORCID, Beaumont Robin N.ORCID, Bradfield Jonathan P., Abraham Abin, Thorleifsson GudmarORCID, Gabrielsen Maiken E., Ostrowski Sisse R.ORCID, Modzelewska Dominika, Nohr Ellen A., Hypponen ElinaORCID, Srivastava Amit, Talbot Octavious, Allard CatherineORCID, Williams Scott M.ORCID, Menon Ramkumar, Shields Beverley M., Sveinbjornsson GardarORCID, Xu Huan, Melbye Mads, Lowe WilliamORCID, Bouchard Luigi, Oken Emily, Pedersen Ole B.ORCID, Gudbjartsson Daniel F.ORCID, Erikstrup ChristianORCID, Sørensen Erik, McCarthy Mark I., Lie Rolv T., Teramo Kari, Hallman Mikko, Juliusdottir Thorhildur, Hakonarson Hakon, Ullum Henrik, Hattersley Andrew T.ORCID, Sletner Line, Merialdi Mario, Rifas-Shiman Sheryl L., Steingrimsdottir Thora, Scholtens DeniseORCID, Power Christine, West JaneORCID, Nyegaard MetteORCID, Capra John A., Skogholt Anne H.ORCID, Magnus Per, Andreassen Ole A.ORCID, Thorsteinsdottir Unnur, Grant Struan F. A.ORCID, Qvigstad Elisabeth, Pennell Craig E.ORCID, Hivert Marie-FranceORCID, Hayes Geoffrey M.ORCID, Jarvelin Marjo-RiittaORCID, McCarthy Mark I., Lawlor Deborah A.ORCID, Nielsen Henriette S.ORCID, Mägi ReedikORCID, Rokas AntonisORCID, Hveem Kristian, Stefansson KariORCID, Feenstra BjarkeORCID, Njolstad PålORCID, Muglia Louis J., Freathy Rachel M.ORCID, Johansson StefanORCID, Zhang Ge, Jacobsson BoORCID, , ,
Abstract
AbstractThe 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 (18,797 cases, 260,246 controls) revealed seven associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 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. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal–fetal relationship between gestational duration and birth weight.
Publisher
Springer Science and Business Media LLC
Reference65 articles.
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