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Biomarker discovery in attention deficit hyperactivity disorder: RNA sequencing of whole blood in discordant twin and case-controlled cohorts
BMC Medical Genomics ( IF 2.1 ) Pub Date : 2020-10-28 , DOI: 10.1186/s12920-020-00808-8
Timothy A. McCaffrey , Georges St. Laurent , Dmitry Shtokalo , Denis Antonets , Yuri Vyatkin , Daniel Jones , Eleanor Battison , Joel T. Nigg

A variety of DNA-based methods have been applied to identify genetic markers of attention deficit hyperactivity disorder (ADHD), but the connection to RNA-based gene expression has not been fully exploited. Using well defined cohorts of discordant, monozygotic twins from the Michigan State University Twin Registry, and case-controlled ADHD cases in adolescents, the present studies utilized advanced single molecule RNA sequencing to identify expressed changes in whole blood RNA in ADHD. Multiple analytical strategies were employed to narrow differentially expressed RNA targets to a small set of potential biomarkers of ADHD. RNA markers common to both the discordant twin study and case-controlled subjects further narrowed the putative targets, some of which had been previously associated with ADHD at the DNA level. The potential role of several differentially expressed genes, including ABCB5, RGS2, GAK, GIT1 and 3 members of the galactose metabolism pathway (GALE, GALT, GALK1) are substantiated by prior associations to ADHD and by established mechanistic connections to molecular pathways relevant to ADHD and behavioral control. The convergence of DNA, RNA, and metabolic data suggests these may be promising targets for diagnostics and therapeutics in ADHD.

中文翻译:

注意缺陷多动障碍中的生物标志物发现:双胞胎和病例对照人群的全血RNA测序

多种基于DNA的方法已被用于识别注意力缺陷多动障碍(ADHD)的遗传标记,但是与基于RNA的基因表达的联系尚未得到充分利用。利用来自密歇根州立大学双生子登记处的不一致,单卵双生子以及青少年中病例对照的ADHD病例的明确定义的队列,本研究利用先进的单分子RNA测序来鉴定ADHD中全血RNA的表达变化。采用多种分析策略将差异表达的RNA靶标缩小为一小部分潜在的ADHD生物标志物。不一致的双胞胎研究和病例对照受试者共同使用的RNA标记进一步缩小了推定的靶标,其中一些以前在DNA水平与ADHD相关。先前与多动症的关联以及与多动症相关分子途径建立的机制联系证实了几种差异表达基因的潜在作用,包括ABCB5,RGS2,GAK,GIT1和半乳糖代谢途径的3个成员(GALE,GALT,GALK1)和行为控制。DNA,RNA和代谢数据的融合表明,这些可能是ADHD诊断和治疗的有希望的目标。
更新日期:2020-10-30
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