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

dc.contributor.authorSolé-Navais, P
dc.contributor.authorFlatley, C
dc.contributor.authorSteinthorsdottir, V
dc.contributor.authorVaudel, M
dc.contributor.authorJuodakis, J
dc.contributor.authorChen, J
dc.contributor.authorLaisk, T
dc.contributor.authorLaBella, AL
dc.contributor.authorWestergaard, D
dc.contributor.authorBacelis, J
dc.contributor.authorBrumpton, B
dc.contributor.authorSkotte, L
dc.contributor.authorBorges, MC
dc.contributor.authorHelgeland, Ø
dc.contributor.authorMahajan, A
dc.contributor.authorWielscher, M
dc.contributor.authorLin, F
dc.contributor.authorBriggs, C
dc.contributor.authorWang, CA
dc.contributor.authorMoen, G-H
dc.contributor.authorBeaumont, RN
dc.contributor.authorBradfield, JP
dc.contributor.authorAbraham, A
dc.contributor.authorThorleifsson, G
dc.contributor.authorGabrielsen, ME
dc.contributor.authorOstrowski, SR
dc.contributor.authorModzelewska, D
dc.contributor.authorNohr, EA
dc.contributor.authorHypponen, E
dc.contributor.authorSrivastava, A
dc.contributor.authorTalbot, O
dc.contributor.authorAllard, C
dc.contributor.authorWilliams, SM
dc.contributor.authorMenon, R
dc.contributor.authorShields, BM
dc.contributor.authorSveinbjornsson, G
dc.contributor.authorXu, H
dc.contributor.authorMelbye, M
dc.contributor.authorLowe, W
dc.contributor.authorBouchard, L
dc.contributor.authorOken, E
dc.contributor.authorPedersen, OB
dc.contributor.authorGudbjartsson, DF
dc.contributor.authorErikstrup, C
dc.contributor.authorSørensen, E
dc.contributor.authorEarly Growth Genetics Consortium
dc.contributor.authorEstonian Biobank Research Team
dc.contributor.authorDanish Blood Donor Study Genomic Consortium
dc.contributor.authorLie, RT
dc.contributor.authorTeramo, K
dc.contributor.authorHallman, M
dc.contributor.authorJuliusdottir, T
dc.contributor.authorHakonarson, H
dc.contributor.authorUllum, H
dc.contributor.authorHattersley, AT
dc.contributor.authorSletner, L
dc.contributor.authorMerialdi, M
dc.contributor.authorRifas-Shiman, SL
dc.contributor.authorSteingrimsdottir, T
dc.contributor.authorScholtens, D
dc.contributor.authorPower, C
dc.contributor.authorWest, J
dc.contributor.authorNyegaard, M
dc.contributor.authorCapra, JA
dc.contributor.authorSkogholt, AH
dc.contributor.authorMagnus, P
dc.contributor.authorAndreassen, OA
dc.contributor.authorThorsteinsdottir, U
dc.contributor.authorGrant, SFA
dc.contributor.authorQvigstad, E
dc.contributor.authorPennell, CE
dc.contributor.authorHivert, M-F
dc.contributor.authorHayes, GM
dc.contributor.authorJarvelin, M-R
dc.contributor.authorMcCarthy, MI
dc.contributor.authorLawlor, DA
dc.contributor.authorNielsen, HS
dc.contributor.authorMägi, R
dc.contributor.authorRokas, A
dc.contributor.authorHveem, K
dc.contributor.authorStefansson, K
dc.contributor.authorFeenstra, B
dc.contributor.authorNjolstad, P
dc.contributor.authorMuglia, LJ
dc.contributor.authorFreathy, RM
dc.contributor.authorJohanson, S
dc.contributor.authorZhang, G
dc.contributor.authorJacobsson, B
dc.date.accessioned2023-04-20T12:28:21Z
dc.date.issued2023-04-03
dc.date.updated2023-04-19T14:43:54Z
dc.description.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 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.en_GB
dc.description.sponsorshipSwedish Research Councilen_GB
dc.description.sponsorshipResearch Council of Norwayen_GB
dc.description.sponsorshipMarch of Dimesen_GB
dc.description.sponsorshipNorwegian Diabetes Associationen_GB
dc.description.sponsorshipNils Normans minnegaveen_GB
dc.description.sponsorshipMedical Research Council (MRC)en_GB
dc.description.sponsorshipBritish Heart Foundationen_GB
dc.description.sponsorshipCHOPen_GB
dc.description.sponsorshipEuropean Regional Development Funden_GB
dc.description.sponsorshipWellcome Trusten_GB
dc.description.sponsorshipRoyal Societyen_GB
dc.description.sponsorshipOak Foundationen_GB
dc.description.sponsorshipFonds de la recherche du Québec en santéen_GB
dc.description.sponsorshipUS National Institutes of Healthen_GB
dc.description.sponsorshipNovo Nordisk Foundationen_GB
dc.format.extent559-567
dc.identifier.citationVol. 55, No. 4, pp. 559-567en_GB
dc.identifier.doihttps://doi.org/10.1038/s41588-023-01343-9
dc.identifier.grantnumber2019-01004en_GB
dc.identifier.grantnumber2015-02559en_GB
dc.identifier.grantnumber547711en_GB
dc.identifier.grantnumber273291en_GB
dc.identifier.grantnumber21-FY16-121en_GB
dc.identifier.grantnumberR01HD101669en_GB
dc.identifier.grantnumber287198en_GB
dc.identifier.grantnumberMR/P014054/1en_GB
dc.identifier.grantnumberAA/18/7/34219en_GB
dc.identifier.grantnumber301178en_GB
dc.identifier.grantnumberCH/F/20/90003en_GB
dc.identifier.grantnumberR01 HD056465en_GB
dc.identifier.grantnumberMOBTP155en_GB
dc.identifier.grantnumberWT104150en_GB
dc.identifier.grantnumberWT220390en_GB
dc.identifier.grantnumberNNF18SA0034956en_GB
dc.identifier.grantnumberNNF14CC0001en_GB
dc.identifier.grantnumberNNF17OC0027594en_GB
dc.identifier.urihttp://hdl.handle.net/10871/132956
dc.identifierORCID: 0000-0003-0750-8248 (Beaumont, Robin N)
dc.identifierORCID: 0000-0001-5620-473X (Hattersley, Andrew T)
dc.identifierORCID: 0000-0003-4152-2238 (Freathy, Rachel M)
dc.language.isoenen_GB
dc.publisherNature Researchen_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pubmed/37012456en_GB
dc.relation.urlhttps://egg-consortium.org/en_GB
dc.relation.urlhttps://www.pgscatalog.org/en_GB
dc.relation.urlhttps://research.23andme.com/dataset-access/en_GB
dc.relation.urlhttp://egg-consortium.org/gestational-duration-2019.htmlen_GB
dc.relation.urlhttp://egg-consortium.org/birth-weight-2019.htmlen_GB
dc.relation.urlhttp://www.geenivaramu.ee/tools/misc_sumstats.zipen_GB
dc.relation.urlhttp://www.nealelab.isen_GB
dc.relation.urlhttps://www.reprogen.orgen_GB
dc.relation.urlhttps://doi.org/10.6084/m9.figshare.c.5304500.v1en_GB
dc.relation.urlhttps://www.finngen.fi/fien_GB
dc.relation.urlhttps://www.repository.cam.ac.uk/handle/1810/283491en_GB
dc.relation.urlhttps://www.finngen.fi/fien_GB
dc.relation.urlhttps://ega-archive.orgen_GB
dc.relation.urlhttps://pan.ukbb.broadinstitute.org/en_GB
dc.relation.urlhttps://data.broadinstitute.org/alkesgroup/LDSCORE/eur_w_ld_chr.tar.bz2en_GB
dc.relation.urlhttps://alkesgroup.broadinstitute.org/LDSCORE/LDSC_SEG_ldscores/Multi_tissue_gene_expr_1000Gv3_ldscores.tgzen_GB
dc.relation.urlhttps://gtexportal.org/home/en_GB
dc.relation.urlhttp://reproductivegenomics.com.au/shiny/endo_eqtl_rna/en_GB
dc.relation.urlhttps://www.omicscience.org/apps/pgwas/en_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/data-hub/genome/GCF_000001405.13/en_GB
dc.relation.urlhttps://github.com/PerinatalLab/metaGWASen_GB
dc.relation.urlhttps://doi.org/10.5281/zenodo.7311977en_GB
dc.relation.urlhttp://hdl.handle.net/10871/137433
dc.rights© The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en_GB
dc.subjectGenetics researchen_GB
dc.subjectGenome-wide association studiesen_GB
dc.titleGenetic effects on the timing of parturition and links to fetal birth weighten_GB
dc.typeArticleen_GB
dc.date.available2023-04-20T12:28:21Z
dc.identifier.issn1061-4036
exeter.place-of-publicationUnited States
dc.descriptionThis is the final version. Available on open access from Nature Research via the DOI in this record. en_GB
dc.descriptionData availability: Cohorts should be contacted individually for access to raw genotype and phenotype data, as each cohort has different data access policies. Summary statistics from the meta-analysis, excluding 23andMe, are available at the EGG website (https://egg-consortium.org/), and access to the weights for constructing the polygenic score of gestational duration excluding 23andMe are available at the PGS Catalog (https://www.pgscatalog.org/, score ID: PGS002806). Access to the full set, including 23andMe results, can be obtained after approval from 23andMe is presented to the corresponding author or by completion of a Data Transfer Agreement (https://research.23andme.com/dataset-access/), which exists to protect the privacy of 23andMe participants. Access to the Danish National Birth Cohort (phs000103.v1.p1), Hyperglycemia and Adverse Pregnancy Outcome (phs000096.v4.p1) and Genomic and Proteomic Network (phs000714.v1.p1) individual-level phenotype and genetic data can be obtained through dbGaP Authorized Access portal (https://dbgap.ncbi.nlm.nih.gov/dbgap/aa/wga.cgi?page=login). The informed consent under which the data or samples were collected is the basis for determining the appropriateness of sharing data through unrestricted-access databases or NIH-designated controlled-access data repositories. The summary statistics used in this publication other than the one generated are available at the following links: fetal GWAS of gestational duration (http://egg-consortium.org/gestational-duration-2019.html), fetal and maternal GWAS of birth weight (http://egg-consortium.org/birth-weight-2019.html), miscarriage (http://www.geenivaramu.ee/tools/misc_sumstats.zip), age at first birth, estradiol (women), endometriosis, number of live births and age at menarche (http://www.nealelab.is), age at menopause (https://www.reprogen.org), testosterone (women)58, SHBG, testosterone and CBAT (https://doi.org/10.6084/m9.figshare.c.5304500.v1), pelvic organ prolapse and leiomyoma of the uterus (https://www.finngen.fi/fi), polycystic ovary syndrome (https://www.repository.cam.ac.uk/handle/1810/283491 and https://www.finngen.fi/fi) and pre-eclampsia (European Genome-phenome Archive, https://ega-archive.org, EGAD00010001984). Pan-UK Biobank data are available at https://pan.ukbb.broadinstitute.org/. Precomputed LD scores for European populations (https://data.broadinstitute.org/alkesgroup/LDSCORE/eur_w_ld_chr.tar.bz2) and multi-tissue gene expression precomputed stratified LD scores (https://alkesgroup.broadinstitute.org/LDSCORE/LDSC_SEG_ldscores/Multi_tissue_gene_expr_1000Gv3_ldscores.tgz) are available. eQTL data from GTEx are available at https://gtexportal.org/home/ and from endometrium at http://reproductivegenomics.com.au/shiny/endo_eqtl_rna/. Protein QTL data were obtained from https://www.omicscience.org/apps/pgwas/. Genome Reference Consortium Human Build 37 (hg19) available at https://www.ncbi.nlm.nih.gov/data-hub/genome/GCF_000001405.13/.en_GB
dc.descriptionCode availability: Code for this project has been structured using a Snakemake workflow65 and is available at https://github.com/PerinatalLab/metaGWAS. A public release of it has been deposited in Zenodo (https://doi.org/10.5281/zenodo.7311977).en_GB
dc.descriptionThe author correction to this article is available in ORE at http://hdl.handle.net/10871/137433
dc.identifier.eissn1546-1718
dc.identifier.journalNature Geneticsen_GB
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_GB
dcterms.dateAccepted2023-02-22
rioxxterms.versionVoRen_GB
rioxxterms.licenseref.startdate2023-04-03
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2023-04-20T10:57:28Z
refterms.versionFCDVoR
refterms.dateFOA2023-04-20T12:28:23Z
refterms.panelAen_GB
refterms.dateFirstOnline2023-04-03


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© The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's licence is described as © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.