Department of Economics and Business Economics

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Xueping Liu, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
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  • Dorte Helenius, Institute of Biological Psychiatry, Sct. Hans Mental Health Center, Copenhagen Mental Health Services, iPSYCH - The Lundbeck Foundation's Initiative for Integrative Psychiatric Research, Boserupvej, DK-4000, Roskilde, Denmark.
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  • Line Skotte, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
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  • Robin N Beaumont, Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
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  • Matthias Wielscher, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; MRC-PHE Centre for Environment, School of Public Health, Imperial College London, London, UK; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
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  • Frank Geller, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
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  • Julius Juodakis, University of Gothenburg
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  • Anubha Mahajan, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
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  • Jonathan P Bradfield, Quantinuum Research, LLC, San Diego, CA, USA.
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  • Frederick T J Lin, Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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  • Suzanne Vogelezang, University Medical Center Rotterdam
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  • Mariona Bustamante, CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain., Universitat Pompeu Fabra, Barcelona Institute for Global Health
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  • Tarunveer S Ahluwalia, COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
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  • Niina Pitkänen, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20520, Turku, Finland.
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  • Carol A Wang, School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Newcastle, NSW, Australia.
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  • Jonas Bacelis, Sahlgrenska University Hospital, Gothenburg
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  • Maria C Borges, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
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  • Ge Zhang, March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, OH, USA., Cincinnati Children's Hospital Medical Center
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  • Bruce A Bedell, Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
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  • Robert M Rossi, March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, OH, USA., University of Cincinnati College of Medicine
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  • Kristin Skogstrand, ipsych, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University, Aarhus, Denmark, Danish Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
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  • Shouneng Peng, Icahn School of Medicine at Mount Sinai
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  • Wesley K Thompson, Institute of Biological Psychiatry, Sct. Hans Mental Health Center, Copenhagen Mental Health Services, iPSYCH - The Lundbeck Foundation's Initiative for Integrative Psychiatric Research, Boserupvej, DK-4000, Roskilde, Denmark.
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  • Vivek Appadurai, Institute of Biological Psychiatry, Sct. Hans Mental Health Center, Copenhagen Mental Health Services, iPSYCH - The Lundbeck Foundation's Initiative for Integrative Psychiatric Research, Boserupvej, DK-4000, Roskilde, Denmark.
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  • Debbie A Lawlor, NIHR Bristol Biomedical Research Centre Nutrition Theme, Bristol, United Kingdom., University of Bristol
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  • Ilkka Kalliala, Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu, 200029 HUS, Finland., Imperial College, London
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  • Christine Power, Population, Policy and Practice, Great Ormond Street Institute for Child Health, University College London, London, UK.
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  • Mark I McCarthy, NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, OX3 7LJ, UK., The University of Oxford
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  • Heather A Boyd, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
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  • Mary L Marazita, University of Pittsburgh
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  • Hakon Hakonarson, The Children's Hospital of Philadelphia, Philadelphia, PA, University of Pennsylvania
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  • M Geoffrey Hayes, Northwestern University Feinberg School of Medicine
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  • Denise M Scholtens, Division of Biostatistics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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  • Fernando Rivadeneira, University Medical Center Rotterdam
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  • Vincent W V Jaddoe, University Medical Center Rotterdam
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  • Rebecca K Vinding, COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
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  • Hans Bisgaard, COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
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  • Bridget A Knight, NIHR Exeter Clinical Research Facility, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
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  • Katja Pahkala, University of Turku
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  • Olli Raitakari, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, 20521, Turku, Finland., University of Turku
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  • Øyvind Helgeland, Norwegian Institute of Public Health, Division of Health data and Digitalization, Department of Genetic Research and Bioinformatics, Oslo, Norway., University of Bergen, Haukeland University Hospital
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  • Stefan Johansson, Haukeland University Hospital, University of Bergen
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  • Pål R Njølstad, Department of Pediatrics, Haukeland University Hospital, Bergen, Norway., University of Bergen
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  • João Fadista, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark, Department of Clinical Sciences, Lund University Diabetes Centre, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
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  • Andrew J Schork, Institute of Biological Psychiatry, Sct. Hans Mental Health Center, Copenhagen Mental Health Services, iPSYCH - The Lundbeck Foundation's Initiative for Integrative Psychiatric Research, Boserupvej, DK-4000, Roskilde, Denmark.
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  • Ron Nudel, Institute of Biological Psychiatry, Sct. Hans Mental Health Center, Copenhagen Mental Health Services, iPSYCH - The Lundbeck Foundation's Initiative for Integrative Psychiatric Research, Boserupvej, DK-4000, Roskilde, Denmark.
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  • Preben Bo Mortensen
  • Anders D Børglum
  • Ole Mors
  • Bo Jacobsson, University of Gothenburg, Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.

Original languageEnglish
Article number3927
JournalNature Communications
Volume10
Issue1
Pages (from-to)1-13
Number of pages13
ISSN2041-1723
DOIs
Publication statusPublished - 2019

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