Correlation of the methylomic signature of smoking during pregnancy with clinical traits in ADHD

Boris Chaumette; Natalie Grizenko; Weam Fageera; Marie-Ève Fortier; Marina Ter-Stepanian; Aurelie Labbe; Ridha Joober

doi:10.1503/jpn.230062

Correlation of the methylomic signature of smoking during pregnancy with clinical traits in ADHD

J Psychiatry Neurosci. 2023 Oct 19;48(5):E390-E399. doi: 10.1503/jpn.230062. Print 2023 Sep-Oct.

Authors

Boris Chaumette¹, Natalie Grizenko¹, Weam Fageera¹, Marie-Ève Fortier¹, Marina Ter-Stepanian¹, Aurelie Labbe¹, Ridha Joober²

Affiliations

¹ From the Douglas Mental Health University Institute, Montréal, Que. (Chaumette, Grizenko, Fageerat, Fortier, Ter-Stepanian, Joober); the Department of Psychiatry, McGill University, Montréal, Que. (Chaumette, Grizenko, Joober); The Neuro, McGill University, Montréal, Que. (Chaumette); the Université Paris Cité, INSERM U1266, Institute of Psychiatry and Neuroscience of Paris, Paris, France (Chaumette); the GHU Paris Psychiatrie & Neurosciences, Paris, France (Chaumette); the Department of Human Genetics, McGill University, Montréal, Que. (Fageera, Joober); the Department of Educational and Counselling Psychology, McGill University, Montréal, Que. (Ter-Stepanian); the Département de Psychoéducation, Université de Sherbrooke, Que. (Ter-Stepanian); the Department of Decision Sciences, HEC Montreal, Montréal, Que. (Labbe); the Department of Neurology and Neurosurgery, McGill University, Montréal, Que. (Joober).
² From the Douglas Mental Health University Institute, Montréal, Que. (Chaumette, Grizenko, Fageerat, Fortier, Ter-Stepanian, Joober); the Department of Psychiatry, McGill University, Montréal, Que. (Chaumette, Grizenko, Joober); The Neuro, McGill University, Montréal, Que. (Chaumette); the Université Paris Cité, INSERM U1266, Institute of Psychiatry and Neuroscience of Paris, Paris, France (Chaumette); the GHU Paris Psychiatrie & Neurosciences, Paris, France (Chaumette); the Department of Human Genetics, McGill University, Montréal, Que. (Fageera, Joober); the Department of Educational and Counselling Psychology, McGill University, Montréal, Que. (Ter-Stepanian); the Département de Psychoéducation, Université de Sherbrooke, Que. (Ter-Stepanian); the Department of Decision Sciences, HEC Montreal, Montréal, Que. (Labbe); the Department of Neurology and Neurosurgery, McGill University, Montréal, Que. (Joober) [email protected].

Abstract

Background: Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent childhood disorder. Maternal smoking during pregnancy is a replicated environmental risk factor for this disorder. It is also a robust modifier of gene methylation during the prenatal developmental period. In this study, we sought to identify loci differentially methylated by maternal smoking during pregnancy and relate their methylation levels to various behavioural and physical outcomes relevant to ADHD.

Methods: We extracted DNA from blood samples from children diagnosed with ADHD and deeply phenotyped. Genome-wide DNA methylation was assessed using Infinium MethylationEPIC BeadChip. Maternal smoking during pregnancy was self-declared and assessed retrospectively.

Results: Our sample included 231 children with ADHD. Statistically significant differences in DNA methylation between children exposed or not to maternal smoking during pregnancy were detected in 3457 CpGs. We kept 30 CpGs with at least 5% of methylation difference between the 2 groups for further analysis. Six genes were associated with varied phenotypes of clinical relevance to ADHD. The levels of DNA methylation in RUNX1 were positively correlated with the CBCL scores, and DNA methylation in MYO1G correlated positively with the score at the Conners rating scale. Methylation level in a CpG located in GFI1 correlated with birthweight, a risk factor for ADHD. Differentially methylated regions were also identified and confirmed the association of RUNX1 methylation levels with the CBCL score.

Limitations: The study has several limitations, including the retrospective recall with self-report of maternal smoking during pregnancy as well as the grouping of individuals of varying age and developmental stage and of both males and females. In addition, the correlation design prevents the building of causation models.

Conclusion: This study provides evidence for the association between the level of methylation at specific loci and quantitative dimensions highly relevant for ADHD as well as birth weight, a measure that has already been associated with increased risk for ADHD. Our results provide further support to public health educational initiatives to stop maternal smoking during pregnancy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Attention Deficit Disorder with Hyperactivity* / genetics
Birth Weight / genetics
Child
Core Binding Factor Alpha 2 Subunit / genetics
DNA Methylation
Female
Humans
Male
Phenotype
Pregnancy
Prenatal Exposure Delayed Effects* / genetics
Retrospective Studies
Smoking / adverse effects
Smoking / genetics

Substances

Core Binding Factor Alpha 2 Subunit

Abstract

Publication types

MeSH terms

Substances

Grants and funding