B3639 - Cell type-specific DNA methylation meta-analysis for ADHD symptoms - 27/10/2020

B number: 
Principal applicant name: 
Dr Doretta Caramaschi | MRC IEU
Mandy Meijer, MSc, Dr Marieke Klein, PhD
Title of project: 
Cell type-specific DNA methylation meta-analysis for ADHD symptoms
Proposal summary: 

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, characterized by symptoms of inattention and/or hyperactivity and impulsivity. Not only people with ADHD experience these symptoms, but also people without ADHD can show these symptoms. The development of ADHD (symptoms) is partially genetic, and can also be influenced by factors in someone’s surrounding, for example prenatal nicotine exposure. Genetics and surrounding factors can interplay and this can be reflected in DNA methylation. Knowing which DNA methylation patterns are associated with ADHD symptoms, can teach us more about the molecular mechanisms underlying ADHD (symptoms). These DNA methylation profiles are cell type-specific. Up to now, most methylome-wide association studies have been performed in whole blood, in which multiple blood cells are present. Because the different blood cells have distinct DNA methylation profiles, it is possible that meaningful signal is cancelled out in whole blood measures. Therefore, we think there might be valuable signal in cell type-specific DNA methylation, done by a statistical method called epigenomic deconvolution. This could give us more insight in the molecular mechanisms of ADHD symptoms.

Impact of research: 
We hope to find robust and specific DNA methylation associations to ADHD symptoms, in the different domains in a cell type-specific manner. This information could lead to the identification of new biomarkers and potential new biological pathways to better understand ADHD-related behaviour.
Date proposal received: 
Tuesday, 20 October, 2020
Date proposal approved: 
Tuesday, 27 October, 2020