Blood miRNA levels associated with ADHD traits in children across six European birth cohorts

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• dc.contributor.author Dypås, Lene B.
• dc.contributor.author Duale, Nur
• dc.contributor.author Olsen, Ann-Karin
• dc.contributor.author Bustamante Pineda, Mariona
• dc.contributor.author Maitre, Léa
• dc.contributor.author Escaramís, Geòrgia
• dc.contributor.author Júlvez Calvo, Jordi
• dc.contributor.author Aguilar Lacasaña, Sofía
• dc.contributor.author Andrušaitytė, Sandra
• dc.contributor.author Casas Sanahuja, Maribel
• dc.contributor.author Vafeiadi, Marina, 1983-
• dc.contributor.author Gražulevičienė, Regina
• dc.contributor.author Heude, Barbara
• dc.contributor.author Lepeule, Johanna
• dc.contributor.author Urquiza, José M.
• dc.contributor.author Wright, John
• dc.contributor.author Yang, Tiffany C.
• dc.contributor.author Vrijheid, Martine
• dc.contributor.author Gützkow, Kristine B.
• dc.date.accessioned 2024-01-09T07:26:44Z
• dc.date.available 2024-01-09T07:26:44Z
• dc.date.issued 2023
• dc.description.abstract Background: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and highly heritable neurodevelopmental disorder of major societal concern. Diagnosis can be challenging and there are large knowledge gaps regarding its etiology, though studies suggest an interplay of genetic and environmental factors involving epigenetic mechanisms. MicroRNAs (miRNAs) show promise as biomarkers of human pathology and novel therapies, and here we aimed to identify blood miRNAs associated with traits of ADHD as possible biomarker candidates and further explore their biological relevance. Methods: Our study population consisted of 1126 children (aged 5-12 years, 46% female) from the Human Early Life Exposome study, a study spanning six ongoing population-based European birth cohorts. Expression profiles of miRNAs in whole blood samples were quantified by microarray and tested for association with ADHD-related measures of behavior and neuropsychological functions from questionnaires (Conner's Rating Scale and Child Behavior Checklist) and computer-based tests (the N-back task and Attention Network Test). Results: We identified 29 miRNAs significantly associated (false discovery rate < .05) with the Conner's questionnaire-rated trait hyperactivity, 15 of which have been linked to ADHD in previous studies. Investigation into their biological relevance revealed involvement in several pathways related to neurodevelopment and function, as well as being linked with other neurodevelopmental or psychiatric disorders known to overlap with ADHD both in symptomology, genetic risk, and co-occurrence, such as autism spectrum disorder or schizophrenia. An additional three miRNAs were significantly associated with Conner's-rated inattention. No associations were found with questionnaire-rated total ADHD index or with computer-based tests. Conclusions: The large overlap of our hyperactivity-associated miRNAs with previous studies on ADHD is intriguing and warrant further investigation. Though this study should be considered explorative and preliminary, these findings contribute towards identifying a set of miRNAs for use as blood-based biomarkers to aid in earlier and easier ADHD diagnosis.
• dc.description.sponsorship Open access funding provided by Norwegian Institute of Public Health (FHI) This work was supported by The Research Council of Norway, NFR-FREE MEDBIO grant, POEMA – POTENTIAL EARLY DIAGNOSTIC MOLECULAR MARKERS OF ADHD: Analysis of miRNA profiles and DNA methylation status in triads (grant no.: 240763/F20). The study received funding from the European Community’s Seventh Framework Programme (FP7/2007–206) under grant agreement no. 308333 (HELIX project) and the H2020-EU.3.1.2. – Preventing Disease Programme under grant agreement no. 874583 (ATHLETE project). The genotyping was supported by the project PI17/01225 and PI17/01935, funded by the Instituto de Salud Carlos III and co-funded by European Union (ERDF, “A way to make Europe”). BiB receives core infrastructure funding from the Wellcome Trust (WT101597MA) and a joint grant from the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) (MR/N024397/1), and has received support from the Human Early Life Exposome (HELIX) (FP7 grant agreement number 308333), the European Union’s Horizon 2020 research and innovation programme (LifeCycle, grant agreement number 733206; ATHLETE, grant agreement number 874583), and National Institute for Health Research Applied Research Collaboration Yorkshire and Humber (NIHR200166). The EDEN study was supported by Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A), and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programmes (FP7/2007–2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l’Education Nationale a complementary health insurance (MGEN), French national agency for food security, French-speaking association for the study of diabetes and metabolism (ALFEDIAM). INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Seyero Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. Kaunas KANC cohort was founded by the European Community’s Seventh Framework Programme (FP7/2007–206) under grant agreement no 308333 (HELIX project), and HORIZON-2020 Programme under grant agreement no. 874583 (ATHLETE project). The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. The Rhea cohort was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU- FP7- HEALTH-2012 Proposal No 308333 HELIX), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15). LM is funded by a Juan de la Cierva-Incorporación fellowship (IJC2018-035394-I) awarded by the Spanish Ministerio de Economía, Industria y Competitividad. JJ holds now the Miguel Servet-II contract (CPII19/00015) awarded by the Instituto de Salud Carlos III (co-funded by the European Social Fund “Investing in your future”). JU is supported by the Spanish regional program PERIS (Ref.: SLT017/20/000119), granted by Departament de Salut de la Generalitat de Catalunya.
• dc.format.mimetype application/pdf
• dc.identifier.citation Dypås LB, Duale N, Olsen AK, Bustamante M, Maitre L, Escaramis G, Julvez J, Aguilar-Lacasaña S, Andrusaityte S, Casas M, Vafeiadi M, Grazuleviciene R, Heude B, Lepeule J, Urquiza J, Wright J, Yang TC, Vrijheid M, Gützkow KB. Blood miRNA levels associated with ADHD traits in children across six European birth cohorts. BMC Psychiatry. 2023 Sep 25;23(1):696. DOI: 10.1186/s12888-023-05199-5
• dc.identifier.doi http://dx.doi.org/10.1186/s12888-023-05199-5
• dc.identifier.issn 1471-244X
• dc.identifier.uri http://hdl.handle.net/10230/58655
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof BMC Psychiatry. 2023 Sep 25;23(1):696
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/240763
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/211250
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/226285
• dc.rights © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword ADHD
• dc.subject.keyword Biomarkers
• dc.subject.keyword Cohort study
• dc.subject.keyword MicroRNA
• dc.title Blood miRNA levels associated with ADHD traits in children across six European birth cohorts
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion