About our research group/lab
Our research
Background
DNA methylation is an epigenetic process that regulates gene activity in response to both genetic and environmental influences, beginning in utero. While methylation plays a key role in healthy development and function, alterations in this process have been linked to the emergence of disease states, including brain-based disorders such as neurodevelopmental, psychiatric and neurological conditions. Thus, DNA methylation may represent a potential biomarker of – or mechanism mediating – genetic and environmental influences on the brain. To test this hypothesis, a growing number of researchers are examining associations between DNA methylation and brain features with the use of MRI, giving rise to the new field of Neuroimaging Epigenetics. So far, however, studies in this field have been very heterogeneous in terms of design, characteristics, and methodology, with few shared practices. Furthermore, results have been typically based on single, cross-sectional studies with small sample sizes – which raises issues of statistical power, low reproducibility and unclear direction of effects. The extent to which methylation associates with individual differences in the living brain therefore remains largely unclear.
Aim
The MIND consortium aims to shed light on the relationship between DNA methylation patterns and brain structure and function across development. We specifically want to help advance the new field of Neuroimaging Epigenetics by (i) promoting collaborative science via multi-cohort analyses; (ii) increasing scientific rigor through data harmonization and the establishment of shared practices; and (iii) elucidating directionality of associations between methylation and the brain via the use of prospective, longitudinal studies across development.
Approach
We combine information on DNA methylation with a wide range of neuroimaging phenotypes measured with MRI from cohorts spanning pregnancy to young adulthood. Such integration within a consortium framework offers new opportunities, but also considerable challenges. In MIND, we reflect on potential strategies that could be used to address those, including applying methods to better isolate developmental changes from technical sources of variability, model time-varying DNAm-brain associations, and reduce high-dimensionality. MIND operates on a federated model, wherein methods, practices, and results are shared among consortium members, while maintaining the confidentiality of the underlying individual-level data. MIND is committed to open science practices, including the use of pre-registration of studies, sharing of analysis scripts, and making full results (e.g., meta-analysis summary statistics) openly accessible. Through these activities, the consortium aims to facilitate an integrative and efficient research environment and to enhance the transparency and reproducibility of our research. 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.
Figure 1. Key challenges in Neuroimaging Epigenetics
Organization and opportunities to join
To date, the MIND consortium comprises a global set of researchers and datasets, including 15 cohorts worldwide from North America, South America, Europe, African and Australia, totaling up to 11,299 participants with DNAm profiles, 10,133 participants with neuroimaging data, and 4,914 participants with both data types for neuroimaging epigenetic analyses. Scientific activities are initiated by researchers and organized by projects. Participating cohorts decide whether to contribute to a MIND project depending on their data, time and interests. Cohorts with genome-wide DNA methylation data (e.g. Illumina 450K or Illumina EPIC chip) and MRI data collected at one or more time points across development (birth to young adulthood) are welcome to join.
Figure 2. World map of sample size per country (overlap DNAm and neuroimaging), as covered by MIND. Sample sizes reflect expected sample sizes after sample processing
Table 1. List of participating cohorts and key contact persons
Cohort | Cohort abbreviation | PMID | Country | Contact person |
Avon Longitudinal Study of Parents and Children | ALSPAC | 22507742 | United Kingdom | Esther Walton |
Brazilian High Risk Cohort | BHRC | 25469819 | Brazil | Rodrigo Grassi-Oliveira |
Drakenstein Child Health Study | DCHS | 317551344 | South-Africa | Dan Stein |
Future of Families and Child Wellbeing Study | FFCWS | 35721627 | United States | Colter Mitchell |
Kids2Health - childhood | Kids2Health | - | Germany | Claudia Buss |
Kids2Health - infancy | Kids2Health | - | Germany | Claudia Buss |
Michigan Twin Neurogenetic Study | MTwiNS | 31466551 | United-States | Luke Hyde |
Oregon ADHD-1000 | Oregon ADHD-1000
|
32066674 | United-States | Michael Mooney |
The CannTeen Study | CannTeen | 35772419 | United Kingdom | Will Lawn, Tom Freeman |
The FinnBrain Birth Cohort Study | FinnBrain | 29025073 | Finland | Tiina Paunio, Jetro Tuurlari |
The Generation R Study | GenR | 28070760 | The Netherlands | Charlotte Cecil |
The Neuroimaging of the Children's Attention Project | NICAP | 26969310 | Australia | Tim Silk |
The Peri/Post-natal Epigenetic Twins Study | PETS | 23171547 | Australia | Jeffrey Craig |
UCIrvine Daily Experiences in Pregnancy Study | UCI cohort | 28842114 | United States | Kieran O'Donnel |
Understanding Pregnancy Signals and Infant Development | UPSIDE | 33795306 | United States | Tom O'Connor |
Key Publications
A systematic review of neuroimaging epigenetic research: calling for an increased focus on development. Walton, E., Baltramonaityte, V., Calhoun, V., Heijmans, B. T., Thompson, P. M., & Cecil, C. A. (2023). Molecular psychiatry, 28(7), 2839-2847.
Consortium Profile: The Methylation, Imaging and NeuroDevelopment (MIND) Consortium. Schuurmans, I. K., Mulder, R. H., Baltramonaityte, V., Lahtinen, A., Qiuyu, F., Melo Rothmann, L., ... & Cecil. (2024). medRxiv, 2024-06.
Our team
Principal Investigator
- Dr Charlotte Cecil, Associate professor of Biological Psychopathology, Erasmus Medical Center
- Dr Esther Walton, Professor in Biological Psychology, University of Bath
Research team
- Dr. Isabel Schuurmans, Postdoctoral researcher in psychiatric epidemiology and omics, Erasmus Medical Center
- Dr. Marlene Staginnus, Postdoctoral researcher in Developmental Psychology, University of Bath
- Dr. Vilte Baltramonaityte, Postdoctoral researcher in Genetic / Epigenetic Psychology, University of Bath