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Biomarker Discovery in Attention Deficit Hyperactivity Disorder: RNA sequencing of Whole Blood in Discordant Twin and Case-Controlled Cohorts

ABSTRACT: Biomarker Discovery in Attention Deficit Hyperactivity Disorder: RNA sequencing of Whole Blood in Discordant Twin and Case-Controlled Cohorts

PROVIDER: PRJNA667703 | ENA |

REPOSITORIES: ENA

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Effect of methylphenidate on gene expression profiles of Attention Deficit Hyperactivity Disorder patients and unaffected controls.

Project description:Attention deficit hyperactivity disorder (ADHD) is a common psychiatric condition of children with a prevalence of 5-10% worldwide. Up to 30% of adults with a history of childhood ADHD maintain symptoms in later life; these adult ADHD patients are severely impaired in social and professional life due to persistence of ADHD core symptoms like impulsivity, attention deficit and hyperactivity as well as frequently observed co-morbidities like alcohol and drug abuse, major depression, bipolar and personality disorders. Pharmaceutical treatment options include methylphenidate (MPH), which is amongst others an inhibitor of the dopamine transporter and therefore increases dopamine levels in the brain. However, not all ADHD patients are MPH responders with clinical features to distinguish responders and non-responders being not at hand so far. Likewise, neurobiological reasons for drug response are still elusive. Here, we examined the global transcriptional response of MPH on lymphoblastoid cell lines (LCLs) derived from ADHD patients and unaffected controls.

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Biomarker Discovery in Attention Deficit Hyperactivity Disorder: RNA sequencing of Whole Blood in Discordant Twin and Case-Controlled Cohorts

Project description:We found 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.

2020-10-07 | GSE159104 | GEO

Effect of methylphenidate on gene expression profiles of Attention Deficit Hyperactivity Disorder patients and unaffected controls.

2014-09-05 | GSE52889 | GEO

Association of epigenetic differences nominated by monozygotic twins discordant for attention-deficit hyperactivity disorder with their brain structures

Project description:The present study examined the relationship between genome-wide methylation differences and variations in brain structures involved in the development of attention-deficit hyperactivity disorder (ADHD). We used monozygotic twins discordant for ADHD to identify candidate DNA methylation sites involved in the development of ADHD. Two pairs of MZ twins discordant for ADHD were recruited from the Department of Child and Adolescent Psychological Medicine at the University of Fukui Hospital. The twins were 9-year-old males (pair 1) and 16-year-old females (pair 2). Genomic DNA was collected from saliva samples, and the DNA was then whole-genome amplified, fragmented, and hybridized to the Human MethylationEPIC BeadChip.

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Association of epigenetic differences nominated by monozygotic twins discordant for attention-deficit hyperactivity disorder with their brain structures

Project description:Association of epigenetic differences nominated by monozygotic twins discordant for attention-deficit hyperactivity disorder with their brain structures

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Biomarker discovery in attention deficit hyperactivity disorder: RNA sequencing of whole blood in discordant twin and case-controlled cohorts.

Project description:BackgroundA 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.MethodsUsing 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.ResultsRNA 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.ConclusionsThe convergence of DNA, RNA, and metabolic data suggests these may be promising targets for diagnostics and therapeutics in ADHD.

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RNA-sequencing data and whole transcriptome analysis from CDH2 knock-in mice, modeling attention-deficit hyperactivity disorder (ADHD)

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