학술논문
Genetic effects on the timing of parturition and links to fetal birth weight
Document Type
Original Paper
Author
Solé-Navais, Pol; Flatley, Christopher; Steinthorsdottir, Valgerdur; Vaudel, Marc; Juodakis, Julius; Chen, Jing; Laisk, Triin; LaBella, Abigail L.; Westergaard, David; Bacelis, Jonas; Brumpton, Ben; Skotte, Line; Borges, Maria C.; Helgeland, Øyvind; Mahajan, Anubha; Wielscher, Matthias; Lin, Frederick; Briggs, Catherine; Wang, Carol A.; Moen, Gunn-Helen; Beaumont, Robin N.; Bradfield, Jonathan P.; Abraham, Abin; Thorleifsson, Gudmar; Gabrielsen, Maiken E.; Ostrowski, Sisse R.; Modzelewska, Dominika; Nohr, Ellen A.; Hypponen, Elina; Srivastava, Amit; Talbot, Octavious; Allard, Catherine; Williams, Scott M.; Menon, Ramkumar; Shields, Beverley M.; Sveinbjornsson, Gardar; Xu, Huan; Melbye, Mads; Lowe, Jr, William; Bouchard, Luigi; Oken, Emily; Pedersen, Ole B.; Gudbjartsson, Daniel F.; Erikstrup, Christian; Sørensen, Erik; Lie, Rolv T.; Teramo, Kari; Hallman, Mikko; Juliusdottir, Thorhildur; Hakonarson, Hakon; Ullum, Henrik; Hattersley, Andrew T.; Sletner, Line; Merialdi, Mario; Rifas-Shiman, Sheryl L.; Steingrimsdottir, Thora; Scholtens, Denise; Power, Christine; West, Jane; Nyegaard, Mette; Capra, John A.; Skogholt, Anne H.; Magnus, Per; Andreassen, Ole A.; Thorsteinsdottir, Unnur; Grant, Struan F. A.; Qvigstad, Elisabeth; Pennell, Craig E.; Hivert, Marie-France; Hayes, Geoffrey M.; Jarvelin, Marjo-Riitta; McCarthy, Mark I.; Lawlor, Deborah A.; Nielsen, Henriette S.; Mägi, Reedik; Rokas, Antonis; Hveem, Kristian; Stefansson, Kari; Feenstra, Bjarke; Njolstad, Pål; Muglia, Louis J.; Freathy, Rachel M.; Johansson, Stefan; Zhang, Ge; Jacobsson, Bo
Source
Nature Genetics. 55(4):559-567
Subject
Language
English
ISSN
1061-4036
1546-1718
1546-1718
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 (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.
Maternal genome-wide analyses identify variants associated with gestational duration and preterm delivery. Maternal alleles positively associated with gestational duration exhibit negative fetal effects on birth weight, likely reflecting antagonistic pleiotropy.
Maternal genome-wide analyses identify variants associated with gestational duration and preterm delivery. Maternal alleles positively associated with gestational duration exhibit negative fetal effects on birth weight, likely reflecting antagonistic pleiotropy.