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

Author

Listed:
  • Xueping Liu

    (Statens Serum Institut)

  • Dorte Helenius

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Mental Health Services Copenhagen)

  • Line Skotte

    (Statens Serum Institut)

  • Robin N. Beaumont

    (University of Exeter, Royal Devon and Exeter Hospital)

  • Matthias Wielscher

    (Imperial College London)

  • Frank Geller

    (Statens Serum Institut)

  • Julius Juodakis

    (University of Gothenburg)

  • Anubha Mahajan

    (University of Oxford)

  • Jonathan P. Bradfield

    (The Children’s Hospital of Philadelphia
    Quantinuum Research, LLC)

  • Frederick T. J. Lin

    (Northwestern University Feinberg School of Medicine)

  • Suzanne Vogelezang

    (University Medical Center Rotterdam
    University Medical Center Rotterdam
    University Medical Center Rotterdam)

  • Mariona Bustamante

    (ISGlobal, Barcelona Institute for Global Health
    Universitat Pompeu Fabra (UPF)
    CIBER Epidemiología y Salud Pública (CIBERESP))

  • Tarunveer S. Ahluwalia

    (University of Copenhagen)

  • Niina Pitkänen

    (University of Turku)

  • Carol A. Wang

    (The University of Newcastle)

  • Jonas Bacelis

    (Sahlgrenska University Hospital)

  • Maria C. Borges

    (MRC Integrative Epidemiology Unit at the University of Bristol
    University of Bristol)

  • Ge Zhang

    (Cincinnati Children’s Hospital Medical Center
    Perinatal Institute, Cincinnati Children’s Hospital Medical Center
    March of Dimes Prematurity Research Center Ohio Collaborative)

  • Bruce A. Bedell

    (University of Iowa)

  • Robert M. Rossi

    (March of Dimes Prematurity Research Center Ohio Collaborative
    University of Cincinnati College of Medicine)

  • Kristin Skogstrand

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Department for Congenital Disorders)

  • Shouneng Peng

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Wesley K. Thompson

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Mental Health Services Copenhagen)

  • Vivek Appadurai

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Mental Health Services Copenhagen)

  • Debbie A. Lawlor

    (MRC Integrative Epidemiology Unit at the University of Bristol
    University of Bristol
    NIHR Bristol Biomedical Research Centre)

  • Ilkka Kalliala

    (Imperial College
    University of Helsinki and Helsinki University Hospital)

  • Christine Power

    (University College London)

  • Mark I. McCarthy

    (University of Oxford
    University of Oxford
    NIHR Oxford Biomedical Research Centre, Churchill Hospital)

  • Heather A. Boyd

    (Statens Serum Institut)

  • Mary L. Marazita

    (University of Pittsburgh
    University of Pittsburgh)

  • Hakon Hakonarson

    (The Children’s Hospital of Philadelphia
    The Children’s Hospital of Philadelphia
    University of Pennsylvania)

  • M. Geoffrey Hayes

    (Northwestern University Feinberg School of Medicine
    Northwestern University
    Northwestern University Feinberg School of Medicine)

  • Denise M. Scholtens

    (Northwestern University Feinberg School of Medicine)

  • Fernando Rivadeneira

    (University Medical Center Rotterdam
    University Medical Center Rotterdam
    University Medical Center Rotterdam)

  • Vincent W. V. Jaddoe

    (University Medical Center Rotterdam
    University Medical Center Rotterdam
    University Medical Center Rotterdam)

  • Rebecca K. Vinding

    (University of Copenhagen)

  • Hans Bisgaard

    (University of Copenhagen)

  • Bridget A. Knight

    (University of Exeter, Royal Devon and Exeter Hospital)

  • Katja Pahkala

    (University of Turku
    University of Turku)

  • Olli Raitakari

    (University of Turku
    Turku University Hospital)

  • Øyvind Helgeland

    (University of Bergen
    Haukeland University Hospital
    Department of Genetic Research and Bioinformatics)

  • Stefan Johansson

    (University of Bergen
    Haukeland University Hospital)

  • Pål R. Njølstad

    (University of Bergen
    Haukeland University Hospital)

  • João Fadista

    (Statens Serum Institut
    Lund University)

  • Andrew J. Schork

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Mental Health Services Copenhagen)

  • Ron Nudel

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Mental Health Services Copenhagen)

  • Daniel E. Miller

    (Cincinnati Children’s Hospital Medical Center)

  • Xiaoting Chen

    (Cincinnati Children’s Hospital Medical Center)

  • Matthew T. Weirauch

    (University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center
    Cincinnati Children’s Hospital)

  • Preben Bo Mortensen

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Aarhus University
    Aarhus University)

  • Anders D. Børglum

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Aarhus University
    Aarhus University)

  • Merete Nordentoft

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Mental Health Services in the Capital Region of Denmark
    University of Copenhagen)

  • Ole Mors

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Aarhus University Hospital)

  • Ke Hao

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Kelli K. Ryckman

    (University of Iowa
    University of Iowa)

  • David M. Hougaard

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Department for Congenital Disorders)

  • Leah C. Kottyan

    (University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center)

  • Craig E. Pennell

    (The University of Newcastle)

  • Leo-Pekka Lyytikainen

    (Fimlab Laboratories
    University of Tampere)

  • Klaus Bønnelykke

    (University of Copenhagen)

  • Martine Vrijheid

    (ISGlobal, Barcelona Institute for Global Health
    Universitat Pompeu Fabra (UPF)
    CIBER Epidemiología y Salud Pública (CIBERESP))

  • Janine F. Felix

    (University Medical Center Rotterdam
    University Medical Center Rotterdam
    University Medical Center Rotterdam)

  • William L. Lowe

    (Northwestern University Feinberg School of Medicine)

  • Struan F. A. Grant

    (The Children’s Hospital of Philadelphia
    The Children’s Hospital of Philadelphia
    University of Pennsylvania)

  • Elina Hyppönen

    (University College London
    University of South Australia Cancer Research Institute
    South Australian Health and Medical Research Institute)

  • Bo Jacobsson

    (University of Gothenburg
    Division of Epidemiology, Norwegian Institute of Public Health)

  • Marjo-Riitta Jarvelin

    (University of Oulu
    Imperial College London)

  • Louis J. Muglia

    (Cincinnati Children’s Hospital Medical Center
    Perinatal Institute, Cincinnati Children’s Hospital Medical Center
    University of Iowa
    University of Cincinnati College of Medicine)

  • Jeffrey C. Murray

    (University of Iowa)

  • Rachel M. Freathy

    (University of Exeter, Royal Devon and Exeter Hospital
    Medical Research Council Integrative Epidemiology Unit at the University of Bristol)

  • Thomas M. Werge

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Mental Health Services Copenhagen
    University of Copenhagen)

  • Mads Melbye

    (Statens Serum Institut
    University of Copenhagen
    Stanford University School of Medicine)

  • Alfonso Buil

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Mental Health Services Copenhagen)

  • Bjarke Feenstra

    (Statens Serum Institut)

Abstract

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.

Suggested Citation

  • Xueping Liu & Dorte Helenius & Line Skotte & Robin N. Beaumont & Matthias Wielscher & Frank Geller & Julius Juodakis & Anubha Mahajan & Jonathan P. Bradfield & Frederick T. J. Lin & Suzanne Vogelezang, 2019. "Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11881-8
    DOI: 10.1038/s41467-019-11881-8
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