PT  - JOURNAL ARTICLE
AU  - Alexander Neumann
AU  - Esther Walton
AU  - Silvia Alemany
AU  - Charlotte Cecil
AU  - Juan Ramon González
AU  - Dereje Demissie Jima
AU  - Jari Lahti
AU  - Samuli T. Tuominen
AU  - Edward D. Barker
AU  - Elisabeth Binder
AU  - Doretta Caramaschi
AU  - Ángel Carracedo
AU  - Darina Czamara
AU  - Jorunn Evandt
AU  - Janine F. Felix
AU  - Bernard F. Fuemmeler
AU  - Kristine B. Gutzkow
AU  - Cathrine Hoyo
AU  - Jordi Julvez
AU  - Eero Kajantie
AU  - Hannele Laivuori
AU  - Rachel Maguire
AU  - Léa Maitre
AU  - Susan K. Murphy
AU  - Mario Murcia
AU  - Pia M. Villa
AU  - Gemma Sharp
AU  - Jordi Sunyer
AU  - Katri Raikkönen
AU  - Marian Bakermans-Kranenburg
AU  - Marinus van IJzendoorn
AU  - Mònica Guxens
AU  - Caroline L. Relton
AU  - Henning Tiemeier
TI  - Association between DNA methylation and ADHD symptoms from birth to school age: A prospective meta-analysis
AID  - 10.1101/806844
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 806844
4099  - http://biorxiv.org/content/early/2019/10/16/806844.short
4100  - http://biorxiv.org/content/early/2019/10/16/806844.full
AB  - Attention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is not known. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation assessment periods: birth and school-age. We examined associations of DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age range 4-15 years) in 2477 children from five cohorts and DNA methylation at school-age with concurrent ADHD symptoms (age 7-11 years) in 2374 children from ten cohorts. The regression estimates at nominal significance of the two EWAS (birth and school-age methylation) correlated (ρ=0.30) between both time points. At birth, we identified nine probes that were associated with later ADHD symptoms at genome-wide significance, including ERC2 and CREB5. Peripheral blood DNA methylation at one of these probes (cg01271805 located in the promotor region of ERC2, which regulates neurotransmitter release) was previously associated with brain methylation. Another genome-wide significant probe (cg25520701) lies within the gene body of CREB5, which was associated with neurite outgrowth and an ADHD diagnosis in previous studies. In contrast, no probes reached genome-wide significance when ADHD was associated with school-age DNA methylation. In conclusion, DNA methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation as biomarker and its involvement in causal pathways.