Dypås, Lene B.Duale, NurOlsen, Ann-KarinBustamante Pineda, MarionaMaitre, LéaEscaramís, GeòrgiaJúlvez Calvo, JordiAguilar Lacasaña, SofíaAndrušaitytė, SandraCasas Sanahuja, MaribelVafeiadi, Marina, 1983-Gražulevičienė, ReginaHeude, BarbaraLepeule, JohannaUrquiza, José M.Wright, JohnYang, Tiffany C.Vrijheid, MartineGützkow, Kristine B.2024-01-092024-01-092023Dypås 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/s12888-023-05199-51471-244Xhttp://hdl.handle.net/10230/58655Background: 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.application/pdfeng© 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s12888-023-05199-5ADHDBiomarkersCohort studyMicroRNAinfo:eu-repo/semantics/openAccess