A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis
Tekijät: Alexander Neumann, Esther Walton, Silvia Alemany, Charlotte Cecil, Juan Ramon González, Dereje D. Jima, Jari Lahti, Samuli T. Tuominen, Edward D. Barker, Elisabeth Binder, Doretta Caramaschi, Ángel Carracedo, Darina Czamara, Jorunn Evandt, Janine F. Felix , Bernard F. Fuemmeler, Kristine B. Gutzkow, Cathrine Hoyo, Jordi Julvez, Eero Kajantie, Hannele Laivuori, Rachel Maguire, Léa Maitre, Susan K. Murphy, Mario Murcia, Pia M. Villa, Gemma Sharp, Jordi Sunyer, Katri Raikkönen, Marian Bakermans-Kranenburg, Marinus van IJzendoorn, Mònica Guxens, Caroline L. Relton, Henning Tiemeier
Kustantaja: SPRINGERNATURE
Julkaisuvuosi: 2020
Journal: Translational Psychiatry
Tietokannassa oleva lehden nimi: TRANSLATIONAL PSYCHIATRY
Lehden akronyymi: TRANSL PSYCHIAT
Artikkelin numero: ARTN 398
Vuosikerta: 10
Numero: 1
Sivujen määrä: 11
ISSN: 2158-3188
eISSN: 2158-3188
DOI: https://doi.org/10.1038/s41398-020-01058-z
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/Publication/51213950
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 unknown. 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 both DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age 4-15 years) in 2477 children from 5 cohorts and of DNA methylation at school age with concurrent ADHD symptoms (age 7-11 years) in 2374 children from 9 cohorts, with 3 cohorts participating at both timepoints. CpGs identified with nominal significance (p < 0.05) in either of the EWAS were correlated between timepoints (rho = 0.30), suggesting overlap in associations; however, top signals were very different. At birth, we identified nine CpGs that predicted later ADHD symptoms (p < 1 x 10(-7)), including ERC2 and CREB5. Peripheral blood DNA methylation at one of these CpGs (cg01271805 in the promoter region of ERC2, which regulates neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene body of CREB5, which previously was associated with neurite outgrowth and an ADHD diagnosis. In contrast, at school age, no CpGs were associated with ADHD with p < 1 x 10(-7). In conclusion, we found evidence in this study that 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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
