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Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium.
Yeung, Edwina; Biedrzycki, Richard J; Gómez Herrera, Laura C; Issarapu, Prachand; Dou, John; Marques, Irene Fontes; Mansuri, Sohail Rafik; Page, Christian Magnus; Harbs, Justin; Khodasevich, Dennis; Poisel, Eric; Niu, Zhongzheng; Allard, Catherine; Casey, Emma; Berstein, Fernanda Morales; Mancano, Giulia; Elliott, Hannah R; Richmond, Rebecca; He, Yiyan; Ronkainen, Justiina; Sebert, Sylvain; Bell, Erin M; Sharp, Gemma; Mumford, Sunni L; Schisterman, Enrique F; Chandak, Giriraj R; Fall, Caroline H D; Sahariah, Sirazul A; Silver, Matt J; Prentice, Andrew M; Bouchard, Luigi; Domellof, Magnus; West, Christina; Holland, Nina; Cardenas, Andres; Eskenazi, Brenda; Zillich, Lea; Witt, Stephanie H; Send, Tabea; Breton, Carrie; Bakulski, Kelly M; Fallin, M Daniele; Schmidt, Rebecca J; Stein, Dan J; Zar, Heather J; Jaddoe, Vincent W V; Wright, John; Grazuleviciene, Regina; Gutzkow, Kristine Bjerve; Sunyer, Jordi.
Afiliação
  • Yeung E; Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
  • Biedrzycki RJ; Division of Intramural Research, Glotech Inc., Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
  • Gómez Herrera LC; ISGlobal, Institute for Global Health, Barcelona, Spain.
  • Issarapu P; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Dou J; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
  • Marques IF; MRC Unit the Gambia at the London School of Hygiene and Tropical Medicine (LSHTM), Banjul, The Gambia.
  • Mansuri SR; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
  • Page CM; Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Harbs J; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Khodasevich D; Genomic Research on Complex Diseases (GRC-Group), CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.
  • Poisel E; Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway.
  • Niu Z; Department of Diagnostics and Intervention, Oncology, Umeå University, Umeå, Sweden.
  • Allard C; Environmental Health Sciences, Berkeley Public Health, CERCH, University of California, Berkeley, California, USA.
  • Casey E; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
  • Berstein FM; Department of Population and Public Health Science, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Mancano G; Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CHUS), Sherbrooke, Quebec, Canada.
  • Elliott HR; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
  • Richmond R; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • He Y; Bristol Medical School Population Health Sciences, University of Bristol, Bristol, UK.
  • Ronkainen J; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Sebert S; Bristol Medical School Population Health Sciences, University of Bristol, Bristol, UK.
  • Bell EM; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Sharp G; Bristol Medical School Population Health Sciences, University of Bristol, Bristol, UK.
  • Mumford SL; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Schisterman EF; Bristol Medical School Population Health Sciences, University of Bristol, Bristol, UK.
  • Chandak GR; Research Unit of Population Health, University of Oulu, Oulu, Finland.
  • Fall CHD; Research Unit of Population Health, University of Oulu, Oulu, Finland.
  • Sahariah SA; Research Unit of Population Health, University of Oulu, Oulu, Finland.
  • Silver MJ; Department of Environmental Health Sciences and Epidemiology and Biostatistics, University at Albany School of Public Health, Albany, New York, USA.
  • Prentice AM; Department of Psychology, University of Exeter, Exeter, UK.
  • Bouchard L; Department of Biostatistics, Epidemiology and Informatics and Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Domellof M; Department of Biostatistics, Epidemiology and Informatics and Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • West C; Genomic Research on Complex Diseases (GRC-Group), CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.
  • Holland N; MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK, UK.
  • Cardenas A; Centre for the Study of Social Change, Mumbai, India.
  • Eskenazi B; MRC Unit the Gambia at the London School of Hygiene and Tropical Medicine (LSHTM), Banjul, The Gambia.
  • Zillich L; MRC Unit the Gambia at the London School of Hygiene and Tropical Medicine (LSHTM), Banjul, The Gambia.
  • Witt SH; Department of Biochemistry and Functional Genomics, Centre intégré Universitaire de santé et de Services Sociaux (CIUSSS) du Saguenay-Lac-St-Jean, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
  • Send T; Department of Laboratory Medicine, CIUSSS du Saguenay-Lac-Saint-Jean - Hôpital de Chicoutimi, Chicoutimi, Quebec, Canada.
  • Breton C; Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
  • Bakulski KM; Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
  • Fallin MD; Environmental Health Sciences, Berkeley Public Health, CERCH, University of California, Berkeley, California, USA.
  • Schmidt RJ; Department of Epidemiology and Population Health, Stanford University, Stanford, California, USA.
  • Stein DJ; Environmental Health Sciences, Berkeley Public Health, CERCH, University of California, Berkeley, California, USA.
  • Zar HJ; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
  • Jaddoe VWV; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
  • Wright J; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
  • Grazuleviciene R; Department of Population and Public Health Science, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Gutzkow KB; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
  • Sunyer J; Dean's Office, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Aging Cell ; : e14194, 2024 May 29.
Article em En | MEDLINE | ID: mdl-38808605
ABSTRACT
Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10-8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article