Epigenome-wide Association Study of Attention-Deficit/Hyperactivity Disorder Symptoms in Adults
Year: 2019
Type: review
Study design: Observational Study
Abstract: BACKGROUND: Previous studies have reported associations between attention-deficit/hyperactivity disorder symptoms and DNA methylation in children. We report the first epigenome-wide association study meta-analysis of adult attention-deficit/hyperactivity disorder symptoms, based on peripheral blood DNA methylation (Infinium HumanMethylation450K array) in three population-based adult cohorts. METHODS: An epigenome-wide association study was performed in the Netherlands Twin Register (N = 2258, mean age 37 years), Dunedin Multidisciplinary Health and Development Study (N = 800, age 38 years), and Environmental Risk Longitudinal Twin Study (N = 1631, age 18 years), and results were combined through meta-analysis (total sample size N = 4689). Region-based analyses accounting for the correlation between nearby methylation sites were also performed. RESULTS: One epigenome-wide significant differentially methylated position was detected in the Dunedin study, but meta-analysis did not detect differentially methylated positions that were robustly associated across cohorts. In region-based analyses, six significant differentially methylation regions (DMRs) were identified in the Netherlands Twin Register, 19 in the Dunedin study, and none in the Environmental Risk Longitudinal Twin Study. Of these DMRs, 92% were associated with methylation quantitative trait loci, and 68% showed moderate to large blood-brain correlations for DNA methylation levels. DMRs included six nonoverlapping DMRs (three in the Netherlands Twin Register, three in the Dunedin study) in the major histocompatibility complex, which were associated with expression of genes in the major histocompatibility complex, including C4A and C4B, previously implicated in schizophrenia. CONCLUSIONS: Our findings point at new candidate loci involved in immune and neuronal functions that await further replication. Our work also illustrates the need for further research to examine to what extent epigenetic associations with psychiatric traits depend on characteristics such as age, comorbidities, exposures, and genetic background.
Source: Biological Psychiatry
Authors: Jenny van Dongen, Nuno R. Zilhão, Karen Sugden, Bastiaan T. Heijmans, Peter A.C. ’t Hoen, Joyce van Meurs, Aaron Isaacs, Rick Jansen, Lude Franke, Dorret I. Boomsma, René Pool, Jenny van Dongen, Jouke J. Hottenga, Marleen M.J. van Greevenbroek, Coen D.A. Stehouwer, Carla J.H. van der Kallen, Casper G. Schalkwijk, Cisca Wijmenga, Lude Franke, Sasha Zhernakova, Ettje F. Tigchelaar, P. Eline Slagboom, Marian Beekman, Joris Deelen, Diana van Heemst, Jan H. Veldink, Leonard H. van den Berg, Cornelia M. van Duijn, Bert A. Hofman, Aaron Isaacs, André G. Uitterlinden, Joyce van Meurs, P. Mila Jhamai, Michael Verbiest, H. Eka D. Suchiman, Marijn Verkerk, Ruud van der Breggen, Jeroen van Rooij, Nico Lakenberg, Hailiang Mei, Maarten van Iterson, Michiel van Galen, Jan Bot, Dasha V. Zhernakova, Rick Jansen, Peter van ’t Hof, Patrick Deelen, Irene Nooren, Peter A.C. ’t Hoen, Bastiaan T. Heijmans, Matthijs Moed, Lude Franke, Martijn Vermaat, Dasha V. Zhernakova, René Luijk, Marc Jan Bonder, Maarten van Iterson, Patrick Deelen, Freerk van Dijk, Michiel van Galen, Wibowo Arindrarto, Szymon M. Kielbasa, Morris A. Swertz, Erik. W. van Zwet, Rick Jansen, Peter-Bram ’t Hoen, Bastiaan T. Heijmans, Eilis J. Hannon, Jonathan Mill, Avshalom Caspi, Jessica Agnew-Blais, Louise Arseneault, David L. Corcoran, Terrie E. Moffitt, Richie Poulton, Barbara Franke, Dorret I. Boomsma
Institutions: Amsterdam Public Health, Vrije Universiteit Amsterdam, Duke University, University of Exeter, Leiden University Medical Center, King's College London, Erasmus MC, Amsterdam UMC Location Vrije Universiteit Amsterdam, University Medical Center Groningen, University of Groningen, University of Otago, Radboud University Nijmegen, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Maastricht University Medical Centre, Maastricht University, University Medical Center Utrecht, Amsterdam Neuroscience, SURFsara (Netherlands)
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,300
Funders: North Carolina Biotechnology Center, American Asthma Foundation, European Commission, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Ministry of Business, Innovation and Employment, Jacobs Foundation, National Institutes of Health, Horizon 2020 Framework Programme, Medical Research Council, Economic and Social Research Council, National Institute on Aging, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1028663679, G1049901796, G1093531541, G1124005961, G1151036099, G1389291084, NeuroLabNL: Optimale condities voor leren en veiligheid van jongeren, G1671364559, G1748805038, G177484282, G1953887145, G2039281854, G2337827486, G2462977380, G2748385693, G2861369480, G2891576335, G2973790809, G3121967442, G3207356259, G3507519538, Neuropsychological and genomic signatures of violence exposure in childhood, G393177772, G4036427723, G408622963, Cohort and Longitudinal Studies Enhancement Resources (CLOSER), G4154018034, G4167878811, G4184501341, G434337789, G4406419128, G4469736514, Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strateg, G4907327099, G4921234783, G4937468798, G5306657525, G536866722, G5464181236, G5598020036, Effects of Nutrition and Lifestyle on Impulsive, Compulsive, and Externalizing behaviours, Persistence and emergence of ADHD in young adulthood: Unravelling aetiology using genetics in a population-based longitudinal cohort, G5701737369, G5702163051, G570796765, G5808246334, G62587543, G6637449936, Mental Health Leadership Fellow - The impact of social relationships in the 21st century on mental health and wellbeing, Netherlands Twin Registry Repository: researching the interplay between genome and environment, Midlife Pace of Aging in the Dunedin Study, G7655969080, G7689122240, G7689853932, G7924559645, G84497985, Aggression subtyping for improved insight and treatment innovation in psychiatric disorders, G8776062500, G8858395165, Aging in 1000 healthy midlife adults: Phase 52 of the Dunedin Study
OpenAlex ID: W2915418295