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Tytuł:
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DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.
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Autorzy:
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van Dongen J; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. .
Hagenbeek FA; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Suderman M; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; MRC Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Roetman PJ; Curium-LUMC, Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Oegstgeest, The Netherlands.
Sugden K; Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.; Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
Chiocchetti AG; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe-Universität, Frankfurt am Main, Germany.
Ismail K; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Mulder RH; Institute of Education and Child Studies, Leiden University, Leiden, The Netherlands.; Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Hafferty JD; Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Adams MJ; Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Walker RM; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Morris SW; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Lahti J; Turku Institute for Advanced Studies, University of Turku, Turku, Finland.; Department of Psychology and logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Küpers LK; University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
Escaramis G; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.; Department of Biomedical Science, Faculty of Medicine and Health Science, University of Barcelona, Barcelona, Spain.; Research Group on Statistics, Econometrics and Health (GRECS), UdG, Girona, Spain.
Alemany S; ISGlobal, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
Jan Bonder M; Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Meijer M; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Ip HF; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Jansen R; Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Baselmans BML; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Parmar P; Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.; Biocenter Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.
Lowry E; Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.; Queen's University Belfast, Belfast, UK.
Streit F; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Sirignano L; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Send TS; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Frank J; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Jylhävä J; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Wang Y; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Mishra PP; Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland.
Colins OF; Curium-LUMC, Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Oegstgeest, The Netherlands.; Department of Special Needs Education, Ghent University, Ghent, Belgium.
Corcoran DL; Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
Poulton R; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand.
Mill J; University of Exeter Medical School, University of Exeter, Exeter, UK.
Hannon E; University of Exeter Medical School, University of Exeter, Exeter, UK.
Arseneault L; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Korhonen T; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Vuoksimaa E; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Felix JF; Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Bakermans-Kranenburg MJ; Clinical Child & Family Studies, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Campbell A; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Czamara D; Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.
Binder E; Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 12 Executive Park Dr, Atlanta, GA, 30329, USA.
Corpeleijn E; University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
Gonzalez JR; ISGlobal, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
Grazuleviciene R; Department of Environmental Sciences, Vytautas Magnus University, K. Donelaicio str. 58, 44248, Kaunas, Lithuania.
Gutzkow KB; Department of Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
Evandt J; Department of Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
Vafeiadi M; Department of Social Medicine, University of Crete, Heraklion, Greece.
Klein M; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.; University Medical Center Utrecht, UMC Utrecht Brain Center, Department of Psychiatry, Utrecht, The Netherlands.
van der Meer D; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
Ligthart L; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Kluft C; Good Biomarker Sciences, Leiden, The Netherlands.
Davies GE; Avera Institute for Human Genetics, 3720 W. 69th Street, Sioux Falls, SD, 57108, USA.
Hakulinen C; Department of Psychology and logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Keltikangas-Järvinen L; Department of Psychology and logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Franke B; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.; Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.
Freitag CM; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe-Universität, Frankfurt am Main, Germany.
Konrad K; University Hospital, RWTH Aachen, Child Neuropsychology Section, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Aachen, Germany.; JARA-Brain Institute II, Molecular Neuroscience and Neuroimaging (INM-11), RWTH Aachen & Research Centre Juelich, Juelich, Germany.
Hervas A; Hospital Universitario Mutua de Terrassa, Child and Adolescent Mental Health Service, Barcelona, Spain.
Fernández-Rivas A; Basurto University Hospital, Psychiatric Service, Osakidetza, Bilbao, Spain.
Vetro A; Szeged University, Department of Pediatrics and Pediatrics health center, Child and Adolescent Psychiatry, Szeged, Hungary.
Raitakari O; Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
Lehtimäki T; Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland.
Vermeiren R; Curium-LUMC, Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Oegstgeest, The Netherlands.; Youz, Parnassia Group, The Hague, The Netherlands.
Strandberg T; Helsinki University Central Hospital, Geriatrics, Helsinki, Finland.
Räikkönen K; Department of Psychology and logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Snieder H; University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
Witt SH; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Deuschle M; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Pedersen NL; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Hägg S; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Sunyer J; ISGlobal, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Franke L; Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Kaprio J; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Ollikainen M; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Moffitt TE; Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.; Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
Tiemeier H; Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Department of Social and Behavioral Science, Harvard TH Chan School of Public Health, Boston, USA.
van IJzendoorn MH; Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, The Netherlands.; Department of Clinical, Educational and Health Psychology, UCL, University of London, London, UK.
Relton C; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; MRC Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Vrijheid M; ISGlobal, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
Sebert S; Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.; Biocenter Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.; Section of Genomics of Common Disease, Department of Medicine, Imperial College London, Hammersmith Hospital Campus, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK.
Jarvelin MR; Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.; Biocenter Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.; MRC-PHE Centre for Environment and Health, Imperial College London, Hammersmith Hospital Campus, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK.
Caspi A; Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.; Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
Evans KL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
McIntosh AM; Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Bartels M; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Boomsma DI; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
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Corporate Authors:
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BIOS Consortium
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Źródło:
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Molecular psychiatry [Mol Psychiatry] 2021 Jun; Vol. 26 (6), pp. 2148-2162. Date of Electronic Publication: 2021 Jan 08.
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Typ publikacji:
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Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals
Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996-
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MeSH Terms:
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DNA Methylation*/genetics
Epigenome*
Adolescent ; Adult ; Aged ; Aggression ; Child ; Child, Preschool ; CpG Islands/genetics ; Epigenesis, Genetic/genetics ; Genome-Wide Association Study ; Humans ; Longevity ; Middle Aged ; Young Adult
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Grant Information:
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MR/R005176/1 United Kingdom MRC_ Medical Research Council; R01 MH062873 United States MH NIMH NIH HHS; U01 NS047537 United States NS NINDS NIH HHS; 230374 International ERC_ European Research Council; R01 AG028555 United States AG NIA NIH HHS; G1002190 United Kingdom MRC_ Medical Research Council; R01 DK103246 United States DK NIDDK NIH HHS; R01 AA012502 United States AA NIAAA NIH HHS; MRF_C0396 United Kingdom MRF MRF; MR/M008924/1 United Kingdom MRC_ Medical Research Council; R01 AG010175 United States AG NIA NIH HHS; R01 AG032282 United States AG NIA NIH HHS; MR/K013807/1 United Kingdom MRC_ Medical Research Council; MR/P005918/1 United Kingdom MRC_ Medical Research Council; MC_UU_00011/5 United Kingdom MRC_ Medical Research Council; R01 HD077482 United States HD NICHD NIH HHS; R01 AG009453 United States AG NIA NIH HHS; 268479 International ERC_ European Research Council; 088806 United Kingdom WT_ Wellcome Trust; MR/J000914/1 United Kingdom MRC_ Medical Research Council; 102215 United Kingdom WT_ Wellcome Trust; N01ES75558 United States ES NIEHS NIH HHS
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Contributed Indexing:
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Investigator: BT Heijmans; PAC 't Hoen; J van Meurs; R Jansen; L Franke; DI Boomsma; R Pool; J van Dongen; JJ Hottenga; MMJ van Greevenbroek; CDA Stehouwer; CJH van der Kallen; CG Schalkwijk; C Wijmenga; L Franke; S Zhernakova; EF Tigchelaar; PE Slagboom; M Beekman; J Deelen; D van Heemst; JH Veldink; LH van den Berg; CM van Duijn; BA Hofman; A Isaacs; AG Uitterlinden; J van Meurs; PM Jhamai; M Verbiest; HED Suchiman; M Verkerk; R van der Breggen; J van Rooij; N Lakenberg; H Mei; M van Iterson; M van Galen; J Bot; DV Zhernakova; R Jansen; P van 't Hof; P Deelen; I Nooren; PAC 't Hoen; BT Heijmans; M Moed; L Franke; M Vermaat; DV Zhernakova; R Luijk; M Jan Bonder; M van Iterson; P Deelen; F van Dijk; M van Galen; W Arindrarto; SM Kielbasa; MA Swertz; EW van Zwet; R Jansen; PB 't Hoen; BT Heijmans
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Entry Date(s):
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Date Created: 20210109 Date Completed: 20211011 Latest Revision: 20231115
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Update Code:
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20240105
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PubMed Central ID:
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PMC8263810
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DOI:
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10.1038/s41380-020-00987-x
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PMID:
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33420481
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DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10 -7 ; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
(© 2021. The Author(s).)
