Genetic effects on the timing of parturition and links to fetal birth weight: [Inkl. Correction]
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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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Nature Genetics |
| Vol/bind | 55 |
| Sider (fra-til) | 559–567 |
| ISSN | 1061-4036 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
B.J. received funding from The Swedish Research Council, Stockholm, Sweden (2015-02559 and 2019-01004), The Research Council of Norway, Oslo, Norway (FRIMEDBIO #547711, #273291) and March of Dimes (#21-FY16-121). Research reported in this publication (B.J., G.Z. and R.M.F.) was supported by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number R01HD101669. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. G.-H.M. has received funding from the Norwegian Diabetes Association and Nils Normans minnegave. G.-H.M. is supported by the Norwegian Research Council (postdoctoral mobility research grant 287198). M.C.B.’s contribution to this work was supported by a UK Medical Research Council (MRC) Skills Development Fellowship (MR/P014054/1) and a University of Bristol Vice-Chancellor’s fellowship. M.C.B. and D.A.L. are supported by the British Heart Foundation (AA/18/7/34219) and work in a Unit that receives funding from the University of Bristol and UK Medical Research Council (MRC) (MC_UU_00011/6). M.V. is supported by the Research Council of Norway (project #301178). D.A.L. is supported by a British Heart Foundation Chair (CH/F/20/90003). S.F.A.G. is supported by Daniel B. Burke Chair for Diabetes Research and NIH Grant R01 HD056465, IDF to CAG center from CHOP; CHOP’s Endowed Chair in Genomic Research. Funding for T.L. was provided by the European Regional Development Fund and the programme Mobilitas Pluss (MOBTP155). B.M.S. is a core member of the NIHR Exeter Clinical Research Facility. R.M.F. and R.N.B. were funded by a Wellcome Trust and Royal Society Sir Henry Dale Fellowship (WT104150). R.M.F. is funded by a Wellcome Trust Senior Research Fellowship (WT220390). B.F. was supported by the Oak Foundation. L.B. is a senior research scholar from the Fonds de la recherche du Québec en santé (FRQS) and member of the CR-CHUS, a FRQS-funded Research Center. E.O. has received funding from the US National Institutes of Health. D.W. is funded by the Novo Nordisk Foundation (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). Additional funding statements for each cohort are available in the Supplementary Note.
Publisher Copyright:
© 2023, The Author(s).
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