DNA methylation associated with persistent ADHD suggests TARBP1 as novel candidate

NEUROPHARMACOLOGY

卷:184

Article

Weiss, Annika L.^1,2  Meijer, Mandy²  Budeus, Bettina¹  Pauper, Marc²  Hakobjan, Marina²  Groothuismink, Johanne²  Shi, Yan²  Neveling, Kornelia²  Buitelaar, Jan K.^3,4,5  Hoogman, Martine²  Franke, Barbara^2,6  Klein, Marieke^2,7,8 

[1] Univ Duisburg Essen, Inst Cell Biol Canc Res, Dept Mol Genet, Essen, Germany

[2] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Human Genet, Med Ctr, Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Donders Ctr Cognit Neuroimaging, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Dept Cognit Neurosci, Med Ctr, Nijmegen, Netherlands

[5] Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands

[6] Radboud Univ Nijmegen, Dept Psychiat, Med Ctr, Nijmegen, Netherlands

[7] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, Utrecht, Netherlands

[8] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

关键词: Max. 6;    DNA methylation;    Epigenetics;    TARBP1;    ADHD;    Smoking;    Neurodevelopmental disorder;   

DOI  :  10.1016/j.neuropharm.2020.108370

来源: Elsevier

【 摘 要 】

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention and/or hyperactivity and impulsivity. ADHD is highly prevalent in childhood and often persists into adulthood. Both genetic variants and environmental factors play a role in the onset and persistence of ADHD, and epigenetic changes, such as DNA methylation are considered as a link for their interplay. To investigate this, we studied DNA methylation in 37 candidate genes by performing targeted bisulfite sequencing of DNA isolated from whole blood of N = 88 individuals diagnosed with adult ADHD and N = 91 unaffected individuals (mean age 34.2 years). Differentially methylated sites were assessed by generalized linear models testing ADHD status and ADHD symptoms, accounting for a methylation-based smoking score, age, sex, and blood cell count. DNA methylation of single sites within DRD4 and KLDR1 was associated with adult ADHD status, and multiple DNA methylation sites within TARBP1 were associated with ADHD symptoms in adulthood and childhood. Awaiting replication, findings of this pilot study point to TARBP1 as a new candidate gene for ADHD symptoms. Our work also stresses the need for research to further examine the effects of environmental factors, such as nicotine exposure, on epigenetic modifications associated with psychiatric traits.

【 授权许可】

Free