Genetic effects on the timing of parturition and links to fetal birth weight.
Pol Sole NavaisChristopher FlatleyValgerdur SteinthorsdottirMarc VaudelJulius JuodakisJing ChenTriin LaiskAbigail Leavitt LaBellaDavid WestergaardJonas BacelisBen Michael BrumptonLine SkotteMaria C BorgesØyvind HelgelandAnubha MahajanMatthias WielscherFrederick T J LinCatherine BriggsCarol A WangGunn-Helen MoenRobin N BeaumontJonathan P BradfieldAbin AbrahamGudmar ThorleifssonMaiken E GabrielsenSisse Rye OstrowskiDominika ModzelewskaEllen A NohrElina HyppӧnenAmit SrivastavaOctavious TalbotCatherine AllardScott M WilliamsRamkumar MenonBeverley M ShieldsGardar SveinbjörnssonHuan XuMads MelbyeWilliam L LoweLuigi BouchardEmily OkenOle Birger Vesterager PedersenDaníel F GuðbjartssonChristian ErikstrupErik Sørensennull nullnull nullnull nullRolv T LieKari TeramoMikko HallmanThorhildur JuliusdottirHakon HakonarsonHenrik UllumAndrew T HattersleyLine SletnerMario MerialdiSheryl L Rifas-ShimanThora SteingrimsdottirDenise M ScholtensChristine PowerJane WestMette NygaardJohn A CapraAnne Heidi SkogholtPer MagnusOle Andreas AndreassenUnnur ThorsteinsdottirStruan F A GrantElisabeth QvigstadCraig E PennellMarie-France HivertM Geoffrey HayesMarjo-Riitta JarvelinMark I McCarthyDeborah A LawlorHenriette Svarre NielsenReedik MägiAntonis RokasKristian HveemKári StefánssonBjarke FeenstraPal Rasmus NjolstadLouis J MugliaRachel M FreathyStefan E JohanssonGe ZhangBo JacobsonPublished in: Nature genetics (2023)
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 six 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.