Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults. To bridge this gap, we established the Methylation, Imaging and NeuroDevelopment (MIND) Consortium, which aims to bring a developmental focus to the emerging field of Neuroimaging Epigenetics by (i) promoting collaborative, adequately powered developmental research via multi-cohort analyses; (ii) increasing scientific rigor through the establishment of shared pipelines and open science practices; and (iii) advancing our understanding of DNA methylation-brain dynamics at different developmental periods (from birth to emerging adulthood), by leveraging data from prospective, longitudinal pediatric studies. MIND currently integrates 15 cohorts worldwide, comprising (repeated) measures of DNA methylation in peripheral tissues (blood, buccal cells, and saliva) and neuroimaging by magnetic resonance imaging across up to five time points over a period of up to 21 years (Npooled DNAm = 11,299; Npooled neuroimaging = 10,133; Npooled combined = 4,914). By triangulating associations across multiple developmental time points and study types, we hope to generate new insights into the dynamic relationships between peripheral DNA methylation and the brain, and how these ultimately relate to neurodevelopmental and psychiatric phenotypes.

The authors have declared no competing interest.

The work of CAMC is supported by the European Unions HorizonEurope Research and Innovation Programme (FAMILY, grant agreement No 101057529; HappyMums, grant agreement No 101057390) and the European Research Council (TEMPO; grant agreement No 101039672). This research was conducted while CAMC was a Hevolution/AFAR New Investigator Awardee in Aging Biology and Geroscience Research. EW and CAMC are supported by the European Unions Horizon 2020 Research and Innovation Programme (EarlyCause, grant agreement No 848158). EW, MS and VB received funding from UK Research and Innovation (UKRI) under the UK governments Horizon Europe / ERC Frontier Research Guarantee [BrainHealth, grant number EP/Y015037/1]. EW also received funding from the National Institute of Mental Health of the National Institutes of Health (award number R01MH113930). We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. This publication is the work of the authors and they will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). The Brazilian High-Risk Cohort Happy Mums is supported by the National Institute of Developmental Psychiatry for Children and Adolescents, a science and technology institute funded by the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq; National Council for Scientific and Technological Development; grant number 573974/2008‐0), Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; Research Support Foundation of the State of Sao Paulo; grant number 2008/57896‐8), and Horizon Health, through the project Understanding, predicting, and treating depression in pregnancy to improve mothers and offspring mental health outcomes (grant number 101057390). The Drakenstein Child Health study is funded by the Bill and Melinda Gates Foundation [grant number OPP 1017641], National Institute on Alcohol Abuse and Alcoholism [grant numbers R21AA023887, R01AA026834-01], US Brain and Behavior Research Foundation [grant number 24467], Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) [grant number U24 AA014811], South African Medical Research Council, UK Governments Newton Fund [grant number NAF002/1001], Wellcome Trust [grant number 203525/Z/16/Z], South Africas National Research Foundation [grant numbers 105865, 120432], ABMRF/The Foundation for Alcohol Research, and Harry Crossley Foundation. FFCW data collection is funded by National Institutes of Health (NIH) R01-HD-036916 and a consortium of other funders. Methylation analyses are funded by the NIH: R01 HD076592, R01 MH103761, R01HL149869, and R01 MD011716. Brain imaging (SAND) is funded by the NIH: R01 MH103761 and R01 MH121079. Kids2health is funded by BMBF 01GL1743A. MTwiNS was supported by funds from the National Institute of Mental Health of the National Institutes of Health (NIH): UH3MH114249 & R01 MD081813; the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the NIH: R01HD093334 & R01 HD104297 & R01 HD066040; the Brain and Behavior Foundation: NARSAD young Investigator Grant, The Avielle Foundation, and Institutional funds from the University of Michigan and Michigan State University. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NIH. The authors would like to thank the staff of the Twin Study of Behavioral and Emotional Development Child (TBED-C) and Michigan Twins Neurogenetics Study (MTwiNS) studies for their hard work, and the authors thank the families who participated in TBED-C and MTwiNS for sharing their lives with us. The Oregon ADHD-1000 cohort is supported by grants from the National Institute of Mental Health of the National Institutes of Health under award numbers R37MH059105 (JTN), R01MH099064 (JTN), R01MH115357 (JTN), R01MH131685 (JTN, MAM). The CannTeen study was funded by the UK Medical Research Council (MR/P012728/1). The FinnBrain study was supported by the Academy of Finland, the Sigrid Juselius Foundation, the Signe and Ane Gyllenberg Foundation, the Jane and Aatos Erkko, and the Foundation and State Grants for Clinical Research (ERVA). The general design of the Generation R Study is made possible by financial support from the Erasmus MC, Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development and the Ministry of Health, Welfare and Sport. The EWAS data were funded by a grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA; project nr. 050-060-810), by funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and by a grant from the National Institute of Child and Human Development (R01HD068437). We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives and pharmacies in Rotterdam. The NICAP cohort is supported by the National Health and Medical Research Council of Australia (NHMRC #1065895 and #2029361) and a grant from the Waterloo Foundation. PETS was supported by grants from the Australian National Health and Medical Research Council (#437015, #607358, #114333), the Bonnie Babes Foundation (#BBF20704), the Financial Markets Foundation for Children (#032-2007), and the Victorian Governments Operational Infrastructure Support Program. The UCIrvine Daily Experiences in Pregnancy Study was funded in part by a European Research Area Network (ERA Net) Neuron grant MecTranGen 01EW1407A to C.B. and National Institutes of Health grants R01 HD-060628 and R01 MD-017387.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees Committees. Consent for biological samples has been collected in accordance with the Human Tissue Act (2004). Informed consent for the use of data collected via questionnaires and clinics was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time. The Scientific Committee and Research Ethical Commission of the Federal University of Rio Grande do Sul, and the Brazilian National Research Ethics Commission (CONEP), approved the protocol and informed consent form in accordance with the Brazilian and international regulatory framework under registration numbers IRB N: 20180018 and CAAE: 74563817.7.1001.5327. The study was approved by the faculty of Health Sciences, Human Research Ethics Committee, University of Cape Town, Stellenbosch University and the Western Cape Provincial Health Research committee. The general design, research aims, and specific measurements of Kids2Health study have been approved by the Medical Ethical Committee of the Ludwig-Maximililans-Universitat Munchen. The study received ethics approval and informed consent from the Institutional Review Boards (IRB) at both Michigan State University and the University of Michigan. The local Institutional Review Board approved the studies for Oregon-ADHD-1000. The study received ethical approval from the University College London (UCL) ethics committee. The study was conducted according to the Declaration of Helsinki and was reviewed and approved by the Ethics Committee of the Hospital District of Southwest Finland (ETMK: 31/180/2011). The general design, research aims, and specific measurements of The Generation R Study have been approved by the Medical Ethical Committee of Erasmus MC, in accordance with the Declaration of Helsinki of the World Medical Association. This study was approved by The Royal Childrens Hospital (RCH) Human Research Ethics Committee (HREC #34071), and parents or guardians gave informed consent while participating children assent. All study procedures were approved by the universitys IRB (UCIrvine), and all participants (pregnant women, and parents on behalf of their infants) provided written informed consent.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors