Journal article
Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration
Nature communications, Vol.10(1), 3927
09/02/2019
DOI: 10.1038/s41467-019-11881-8
PMCID: PMC6718389
PMID: 31477735
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
). 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.
Details
- Title: Subtitle
- Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration
- Creators
- Xueping Liu - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, DenmarkDorte Helenius - Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, DenmarkKelli K Ryckman - Department of Epidemiology, University of Iowa, Iowa City, IA, USAJeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, IA, USALine Skotte - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, DenmarkRobin 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, UKMatthias Wielscher - Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UKFrank Geller - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, DenmarkJulius Juodakis - Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenAnubha Mahajan - Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UKJonathan P Bradfield - Quantinuum Research, LLC, San Diego, CA, USAFrederick T J Lin - Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USASuzanne Vogelezang - Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsMariona Bustamante - CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, SpainTarunveer S Ahluwalia - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, DenmarkNiina Pitkänen - Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20520, Turku, FinlandCarol A Wang - School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Newcastle, NSW, AustraliaJonas Bacelis - Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, SwedenMaria C Borges - Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKGe Zhang - March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, OH, USABruce A Bedell - Department of Pediatrics, University of Iowa, Iowa City, IA, USARobert M Rossi - Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USAKristin Skogstrand - Statens Serum Institut, Center for Neonatal Screening, Department for Congenital Disorders, Copenhagen, DenmarkShouneng Peng - Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USAWesley K Thompson - Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, DenmarkVivek Appadurai - Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, DenmarkDebbie A Lawlor - NIHR Bristol Biomedical Research Centre, Bristol, UKIlkka Kalliala - Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu, 200029 HUS, FinlandChristine Power - Population, Policy and Practice, Great Ormond Street Institute for Child Health, University College London, London, UKMark I McCarthy - NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, OX3 7LJ, UKHeather A Boyd - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, DenmarkMary L Marazita - Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USAHakon Hakonarson - Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USAM Geoffrey Hayes - Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USADenise M Scholtens - Division of Biostatistics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USAFernando Rivadeneira - Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsVincent W V Jaddoe - Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsRebecca K Vinding - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, DenmarkHans Bisgaard - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, DenmarkBridget 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, UKKatja Pahkala - Paavo Nurmi Centre, Sports & Exercise Medicine Unit, Department of Health and Physical Activity, University of Turku, 20520, Turku, FinlandOlli Raitakari - Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, 20521, Turku, FinlandØyvind Helgeland - Norwegian Institute of Public Health, Division of Health data and Digitalization, Department of Genetic Research and Bioinformatics, Oslo, NorwayStefan Johansson - Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, NorwayPål R Njølstad - Department of Pediatrics, Haukeland University Hospital, Bergen, NorwayJoão Fadista - Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, SwedenAndrew J Schork - Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, DenmarkRon Nudel - Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, DenmarkDaniel E Miller - Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USAXiaoting Chen - Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USAMatthew T Weirauch - Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital, Cincinnati, OH, USAPreben Bo Mortensen - iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, DenmarkAnders D Børglum - Department of Biomedicine-Human Genetics, Aarhus University, Aarhus, DenmarkMerete Nordentoft - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkOle Mors - Psychosis Research Unit, Aarhus University Hospital, Risskov, DenmarkKe Hao - Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USADavid M Hougaard - Statens Serum Institut, Center for Neonatal Screening, Department for Congenital Disorders, Copenhagen, DenmarkLeah C Kottyan - Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USACraig E Pennell - School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Newcastle, NSW, AustraliaLeo-Pekka Lyytikainen - Department of Clinical Chemistry, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, 33014, Tampere, FinlandKlaus Bønnelykke - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, DenmarkMartine Vrijheid - CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, SpainJanine F Felix - Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsWilliam L Lowe Jr - Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USAStruan F A Grant - Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USAElina Hyppönen - South Australian Health and Medical Research Institute, Adelaide, AustraliaBo Jacobsson - Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, NorwayMarjo-Riitta Jarvelin - Department of Epidemiology and Biostatistics, School of Public Health, Medical Research Council-Health Protection Agency Centre for Environment and Health, Faculty of Medicine, Imperial College London, London, UKLouis J Muglia - Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USARachel M Freathy - Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UKThomas M Werge - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkMads Melbye - Department of Medicine, Stanford University School of Medicine, Stanford, CA, USAAlfonso Buil - Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, DenmarkBjarke Feenstra - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. fee@ssi.dk
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.10(1), 3927
- DOI
- 10.1038/s41467-019-11881-8
- PMID
- 31477735
- PMCID
- PMC6718389
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Grant note
- MC_UU_00011/6 / Medical Research Council Wellcome Trust 106130 / Wellcome Trust R01 NS099068 / NINDS NIH HHS U01 DK105535 / NIDDK NIH HHS 093831 / Wellcome Trust R01 DK103246 / NIDDK NIH HHS 203141 / Wellcome Trust R01 GM055479 / NIGMS NIH HHS P30 AR070549 / NIAMS NIH HHS R01 HD091527 / NICHD NIH HHS 090532 / Wellcome Trust
- Language
- English
- Date published
- 09/02/2019
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984214814502771
Metrics
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