Epigenetic signature for attention-deficit/hyperactivity disorder: identification of miR-26b-5p, miR-185-5p, and miR-191-5p as potential biomarkers in peripheral blood mononuclear cells.,Neuropsychopharmacology

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Epigenetic signature for attention-deficit/hyperactivity disorder: identification of miR-26b-5p, miR-185-5p, and miR-191-5p as potential biomarkers in peripheral blood mononuclear cells.
Neuropsychopharmacology ( IF 6.6 ) Pub Date : 2018-12-19 , DOI: 10.1038/s41386-018-0297-0
Cristina Sánchez-Mora _{1,

2,

3} , María Soler Artigas _{1,

2,

3} , Iris Garcia-Martínez _{1,

2} , Mireia Pagerols _{1,

2} , Paula Rovira _{1,

2} , Vanesa Richarte _{2,

3,

4} , Montse Corrales _{2,

3,

4} , Christian Fadeuilhe ₂ , Natàlia Padilla _{5,

6} , Xavier de la Cruz _{5,

6,

7} , Barbara Franke _{8,

9} , Alejandro Arias-Vásquez _{8,

9} , Miguel Casas _{1,

2,

3,

4} , Josep-Antoni Ramos-Quiroga _{1,

2,

3,

4} , Marta Ribasés _{1,

2,

3}

Affiliation

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood and persists into adulthood in 40-65% of cases. Given the polygenic and heterogeneous architecture of the disorder and the limited overlap between genetic studies, there is a growing interest in epigenetic mechanisms, such as microRNAs, that modulate gene expression and may contribute to the phenotype. We attempted to clarify the role of microRNAs in ADHD at a molecular level through the first genome-wide integrative study of microRNA and mRNA profiles in peripheral blood mononuclear cells of medication-naive individuals with ADHD and healthy controls. We identified 79 microRNAs showing aberrant expression levels in 56 ADHD cases and 69 controls, with three of them, miR-26b-5p, miR-185-5p, and miR-191-5p, being highly predictive for diagnostic status in an independent dataset of 44 ADHD cases and 46 controls. Investigation of downstream microRNA-mediated mechanisms underlying the disorder, which was focused on differentially expressed, experimentally validated target genes of the three highly predictive microRNAs, provided evidence for aberrant myo-inositol signaling in ADHD and indicated an enrichment of genes involved in neurological disease and psychological disorders. Our comprehensive study design reveals novel microRNA-mRNA expression profiles aberrant in ADHD, provides novel insights into microRNA-mediated mechanisms contributing to the disorder, and highlights promising candidate peripheral biomarkers.

中文翻译：

注意力缺陷/多动障碍的表观遗传特征：鉴定 miR-26b-5p、miR-185-5p 和 miR-191-5p 作为外周血单核细胞的潜在生物标志物。

注意力缺陷/多动障碍 (ADHD) 是儿童时期最常见的神经发育障碍之一，40-65% 的病例会持续到成年。鉴于该疾病的多基因和异质结构以及遗传研究之间有限的重叠，人们对表观遗传机制越来越感兴趣，例如调节基因表达并可能有助于表型的微小RNA。我们试图通过首次对未接受药物治疗的 ADHD 患者和健康对照者的外周血单核细胞中的 microRNA 和 mRNA 谱进行全基因组综合研究，在分子水平上阐明 microRNA 在 ADHD 中的作用。我们鉴定出 79 个 microRNA 在 56 个 ADHD 病例和 69 个对照中表现出异常表达水平，其中 3 个：miR-26b-5p、miR-185-5p 和 miR-191-5p，在独立数据集中高度预测诊断状态44 例 ADHD 病例和 46 例对照。对下游 microRNA 介导的疾病机制的研究，重点是三种高度预测性 microRNA 的差异表达、经过实验验证的靶基因，为 ADHD 中异常的肌醇信号传导提供了证据，并表明与神经系统疾病和疾病相关的基因富集。心理障碍。我们的综合研究设计揭示了 ADHD 中异常的新型 microRNA-mRNA 表达谱，提供了对 microRNA 介导的导致该疾病的机制的新见解，并强调了有前途的候选外周生物标志物。

更新日期：2019-01-26

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