SynthesisCommunications biology2024
A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation.
Open access · goldAbstract readMeta-Analysis
In one paragraph
Synthesis in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
5.5field-weighted citation impact, top 6% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed, 5 citations in OpenAlex.
- Immune pathways and prenatal/perinatal environmental exposures contribute to epigenetic gestational age prediction and acceleration.Epigenetics · 2026Article
- Cohort Profile Update: The Finnish Gestational Diabetes (FinnGeDi) study.International journal of epidemiology · 2026Article
- A first-born twin has a higher risk of acute leukemia in a population-based assessment of cancer in twins in California, and a lower than anticipated rate of twin concordance.Haematologica · 2025Article
- Editorial: Prenatal environmental and genetic interactions: an exploration from fetal development to child health.Frontiers in pediatrics · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
66 authors at 20 institutions in 13 countries.
Shaobo LiCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, USA.ORCID 0000-0002-0544-5338
Natalia SpitzEpigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France.ORCID 0000-0003-4776-1758
Akram GhantousEpigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France.
Sarina AbrishamcarDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.ORCID 0000-0001-9478-7374
Brigitte ReimannCentre for Environmental Sciences, UHasselt, Agoralaan, Building D, 3590, Diepenbeek, Belgium.
Irene MarquesThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Matt J SilverMedical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, London, UK.ORCID 0000-0002-9636-0144
Sofía Aguilar-LacasañaISGlobal, Institute for Global Health, Barcelona, Spain.
Negusse KitabaHuman Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton, UK.ORCID 0000-0001-7518-9096
Faisal I RezwanHuman Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton, UK.ORCID 0000-0001-9921-222X
Stefan RöderDepartment of Environmental Immunology, Helmholtz Centre for Environmental Research -UFZ, Leipzig, Germany.ORCID 0000-0001-9367-663X
Lea SirignanoDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Johanna TuhkanenDepartment of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
Giulia MancanoMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Gemma C SharpMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Catherine MetayerSchool of Public Health, University of California Berkeley, Berkeley, California, USA.
Libby MorimotoSchool of Public Health, University of California Berkeley, Berkeley, California, USA.ORCID 0000-0002-1509-739X
Dan J SteinSAMRC Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry & Neuroscience Institute, University of Cape Town, Rondebosch, South Africa.ORCID 0000-0001-7218-7810
Heather J ZarSAMRC Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry & Neuroscience Institute, University of Cape Town, Rondebosch, South Africa.
Rossella AlfanoCentre for Environmental Sciences, UHasselt, Agoralaan, Building D, 3590, Diepenbeek, Belgium.ORCID 0000-0001-9374-4727
Tim NawrotCentre for Environmental Sciences, UHasselt, Agoralaan, Building D, 3590, Diepenbeek, Belgium.
Congrong WangCentre for Environmental Sciences, UHasselt, Agoralaan, Building D, 3590, Diepenbeek, Belgium.
Eero KajantieClinical Medicine Research Unit, Medical Research Center Oulu, Oulu University, Hospital and University of Oulu, Oulu, Finland.ORCID 0000-0001-7081-8391
Elina KeikkalaClinical Medicine Research Unit, Medical Research Center Oulu, Oulu University, Hospital and University of Oulu, Oulu, Finland.
Sanna MustaniemiClinical Medicine Research Unit, Medical Research Center Oulu, Oulu University, Hospital and University of Oulu, Oulu, Finland.ORCID 0000-0003-4483-830X
Justiina RonkainenResearch Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland.ORCID 0000-0001-7375-8099
Sylvain SebertResearch Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland.ORCID 0000-0001-6681-6983
Wnurinham SilvaResearch Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland.ORCID 0000-0001-8129-890X
Marja VääräsmäkiClinical Medicine Research Unit, Medical Research Center Oulu, Oulu University, Hospital and University of Oulu, Oulu, Finland.
Vincent W V JaddoeThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.ORCID 0000-0003-2939-0041
Robin M BernsteinDepartment of Anthropology and Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO, USA.
Andrew M PrenticeMRC Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia.ORCID 0000-0001-5389-451X
Marta Cosin-TomasISGlobal, Institute for Global Health, Barcelona, Spain.
Terence DwyerNuffield Department of Women's & Reproductive Health, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.ORCID 0000-0002-2091-7663
Siri Eldevik HåbergCentre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Zdenko HercegEpigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France.
Maria C MagnusCentre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Monica Cheng Munthe-KaasDepartment of Pediatric Oncology and Hematology, Oslo University Hospital, Norwegian Institute of Public Health, Oslo, Norway.
Christian M PageCentre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Maja VölkerDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Maria GillesDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Tabea SendDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Stephanie WittDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.ORCID 0000-0002-1571-1468
Lea ZillichDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.ORCID 0000-0001-7457-374X
Luigi GagliardiWoman and Child Health Department, Ospedale Versilia, AUSL Toscana Nord Ovest, Pisa, Italy.
Lorenzo RichiardiDepartment of Medical Sciences, University of Turin, CPO Piemonte, Turin, Italy.
Darina CzamaraDepartment of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.ORCID 0000-0001-7381-904X
Katri RäikkönenDepartment of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
Lida ChatziDepartment of Population and Public Health Sciences, Keck School of Medicine of USC. University of Southern California, Los Angeles, CA, USA.
Marina VafeiadiDepartment of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece.ORCID 0000-0002-6143-7172
S Hasan ArshadClinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Susan EwartCollege of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
Michelle PlusquinCentre for Environmental Sciences, UHasselt, Agoralaan, Building D, 3590, Diepenbeek, Belgium.
Janine F FelixThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.ORCID 0000-0002-9801-5774
Sophie E MooreDepartment of Women & Children's Health, King's College London, London, UK.
Martine VrijheidISGlobal, Institute for Global Health, Barcelona, Spain.ORCID 0000-0002-7090-1758
John W HollowayHuman Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton, UK.ORCID 0000-0001-9998-0464
Wilfried KarmausDivision of Epidemiology, Biostatistics, and Environmental Health, University of Memphis, Memphis, TN, USA.ORCID 0000-0003-2684-1492
Gunda HerberthDepartment of Environmental Immunology, Helmholtz Centre for Environmental Research -UFZ, Leipzig, Germany.ORCID 0000-0003-0212-3509
Ana ZenclussenDepartment of Environmental Immunology, Helmholtz Centre for Environmental Research -UFZ, Leipzig, Germany.ORCID 0000-0003-3544-4552
Fabian StreitDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.ORCID 0000-0003-1080-4339
Jari LahtiDepartment of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-4310-5297
Anke HülsDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Thanh T HoangEpidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.ORCID 0000-0002-8498-0020
Stephanie J LondonEpidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.ORCID 0000-0003-4911-5290
Joseph L WiemelsCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, USA. wiemels@usc.edu.ORCID 0000-0003-4838-9951
Heidelberg University · DEHasselt University · BEUniversity of Helsinki · FICentre international de recherche sur le cancer · FRErasmus MC · NLHelmholtz Centre for Environmental Research · DENorwegian Institute of Public Health · NOOulu University Hospital · FIUniversity of Oulu · FIUniversity of Southern California · USBerkeley Public Health Division · USEmory University · USNational Institutes of Health · USSouth African Medical Research Council · ZASouthampton General Hospital · GBUniversitat Pompeu Fabra · ESAberystwyth University · GBBarcelona Institute for Global Health · ESDavid Hide Asthma and Allergy Research Centre · GBJohn Radcliffe Hospital · GB
Funding
Environmental and Molecular Epidemiology of Childhood LeukemiaR01ES009137 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI METAYER, CATHERINE · 1999 to 2013
$21.1MGenetic And Environmental Factors In Childhood Respiratory HealthZIAES049019 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI LONDON, STEPHANIE · 2009 to 2025
$6.8MProject 3: Prenatal Exposure, DNA Methylation & Childhood LeukemiaP01ES018172 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI METAYER, CATHERINE · 2009 to 2013
$3.7MImpact of low IL-10 levels at birth and leukemia riskR01CA185058 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KOGAN, SCOTT C., WIEMELS, JOSEPH LEO · 2014 to 2018
$3.1MPerinatal immune development and risk of childhood acute lymphoblastic leukemiaR01CA175737 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MA, XIAOMEI, WIEMELS, JOSEPH LEO · 2014 to 2018
$3.0MMedical Research Council MC_EX_MR/M01424X/1Medical Research Council MC_PC_21037Medical Research Council MC_PC_MR/R020183/1Medical Research Council MC_U123292701Medical Research Council MC_UP_1005/1Medical Research Council MC_UU_00026/3Medical Research Council MR/P012019/1Medical Research Council MR/T032863/1NCI NIH HHS R01 CA175737NCI NIH HHS R01 CA185058NIEHS NIH HHS P01 ES018172NIEHS NIH HHS R01 ES009137World Health Organization 001
Abstract
Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.
Indexed as
Birth OrderDNA MethylationChildEpigenesis, GeneticEpigenomicsFemaleHumansInfant, NewbornPregnancy
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