Associations Between Blood Leukocyte DNA Methylation and Sustained Attention in Mid-To-Late Childhood

Abstract

Aims: To identify associations between DNA methylation (DNAm) across the epigenome and symptoms related to attention-deficit/hyperactivity disorder in a population of Hispanic children. Materials & methods: Among 517 participants in the ELEMENT study aged 9–18 years, we conducted an epigenome-wide association study examining associations between blood leukocyte DNAm and performance on the Conners’ continuous performance test (CPT3). Results: DNAm at loci in or near ZNF814, ELF4 and OR6K6 and functional enrichment for gene pathways pertaining to ferroptosis, inflammation, immune response and neurotransmission were significantly related to CPT3 scores. Conclusion: DNAm was associated with CPT3 performance. Further analysis is warranted to understand how these genes and enriched pathways contribute to attention-deficit/hyperactivity disorder.

Keywords::

• adolescent health
• child health
• DNA methylation
• epigenetic epidemiology
• epigenetics
• neurobehavior
• neurodevelopment

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2023-0169

Author contributions

J Ehlinger conceived the idea for the project, performed the data analysis and wrote the manuscript. JM Goodrich supervised the project, contributed to study conception and design, and generated epigenetic data. MM Téllez-Rojo and KE Peterson designed, maintained and led the ELEMENT cohort. A Cantoral and A Mercado-García acquired cohort data. DJ Watkins contributed expertise to interpret data. MM Téllez-Rojo, KE Peterson, DC Dolinoy and JM Goodrich acquired funding for the study. All authors contributed to the drafting of the manuscript and approve the final version.

Acknowledgments

We would like to acknowledge the contributions of and express our deepest gratitude to the American British Cowdray Medical Center in Mexico for graciously allowing us to use their research facilities making this work possible. We would also like to gratefully acknowledge the tireless work of the ELEMENT research staff for their persistent work in data collection, sample preparation and experimental proceedings. We recognize the Bioinformatics Core and the Advanced Genomics Core of the University of Michigan Medical School’s Biomedical Research Core Facilities in their support of this research. Lastly, we extend our appreciation to all the cohort participants, for without their contribution none of this research would have been possible.

Financial disclosure

This ELEMENT study received funding from the US Environmental Protection Agency (grant no. RD83543601) and National Institute of Environmental Health Sciences (award nos. P01 ES02284401, R01 ES007821, R01 ES014930, R01 ES013744, P30 ES017885, 1U2C ES026553, K01 HL151673 and R35 ES031686). This study was also supported and partially funded by the National Institute of Public Health/Ministry of Health of Mexico. J Ehlinger is also supported by National Institute of Environmental Health Sciences under the Environmental Toxicology and Epidemiology training grant (award no. T32 ES007062). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Researchers affirm that all research protocols were approved by the institutional review boards of the University of Michigan and the Mexico National Institute of Public Health.

They also attest that both informed consent and participant assent were obtained from the parents of all participants.

Data sharing statement

Data (epigenetic and demographic) from the ELEMENT study are available through the NIH Human Health Exposure Analysis Resource data repository (doi: 10.36043/1431_392, 10.36043/1431_327 and 10.36043/1431_393). Additional data are available upon request from the study team.