Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree.
paper
Cited
Public
Unavailable
- Authors
- Lesch, K-P; Selch, S; Renner, T J; Jacob, C; Nguyen, T T; Hahn, T; Romanos, M; Walitza, S; Shoichet, S; Dempfle, A; Heine, M; Boreatti-HΓΌmmer, A; Romanos, J; Gross-Lesch, S; Zerlaut, H; Wultsch, T; Heinzel, S; Fassnacht, M; Fallgatter, A; Allolio, B; SchΓ€fer, H; Warnke, A; Reif, A; Ropers, H-H; Ullmann, R
- Year
- 2011
- Journal
- Molecular psychiatry
- PMID
- 20308990
- DOI
- 10.1038/mp.2010.29
Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental syndrome characterized by hyperactivity, inattention and increased impulsivity. To detect micro-deletions and micro-duplications that may have a role in the pathogenesis of ADHD, we carried out a genome-wide screen for copy number variations (CNVs) in a cohort of 99 children and adolescents with severe ADHD. Using high-resolution array comparative genomic hybridization (aCGH), a total of 17 potentially syndrome-associated CNVs were identified. The aberrations comprise 4 deletions and 13 duplications with approximate sizes ranging from 110βkb to 3βMb. Two CNVs occurred de novo and nine were inherited from a parent with ADHD, whereas five are transmitted by an unaffected parent. Candidates include genes expressing acetylcholine-metabolizing butyrylcholinesterase (BCHE), contained in a de novo chromosome 3q26.1 deletion, and a brain-specific pleckstrin homology domain-containing protein (PLEKHB1), with an established function in primary sensory neurons, in two siblings carrying a 11q13.4 duplication inherited from their affected mother. Other genes potentially influencing ADHD-related psychopathology and involved in aberrations inherited from affected parents are the genes for the mitochondrial NADH dehydrogenase 1 Ξ± subcomplex assembly factor 2 (NDUFAF2), the brain-specific phosphodiesterase 4D isoform 6 (PDE4D6) and the neuronal glucose transporter 3 (SLC2A3). The gene encoding neuropeptide Y (NPY) was included in a βΌ3βMb duplication on chromosome 7p15.2-15.3, and investigation of additional family members showed a nominally significant association of this 7p15 duplication with increased NPY plasma concentrations (empirical family-based association test, P=0.023). Lower activation of the left ventral striatum and left posterior insula during anticipation of large rewards or losses elicited by functional magnetic resonance imaging links gene dose-dependent increases in NPY to reward and emotion processing in duplication carriers. These findings implicate CNVs of behaviour-related genes in the pathogenesis of ADHD and are consistent with the notion that both frequent and rare variants influence the development of this common multifactorial syndrome.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
No citations found.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Neuroprotection by canagliflozin in a Huntington's disease model: role of HIF-1Ξ± and PI3K/AKT signaling. | Elgindy AM et al. | β | 2026 | β |
| Powering the mind: deciphering the shared genetic architecture between mitochondrial DNA copy number and major psychiatric disorders. | Xue H et al. | β | 2026 | β |
| Relationship Between MOXO-D-CPT Results and Volumetric Brain MR in Attention Deficit Hyperactivity Disorder. | TarlacΔ± S et al. | β | 2026 | β |
| Altered Co-Expression Patterns of Mitochondrial NADH-Dehydrogenase Genes in the Prefrontal Cortex of Rodent ADHD Models. | Sylko PA et al. | β | 2025 | β |
| Hyperactivity and Differential Gene Expression in <i>lbx1a<sup>(</sup><sup>-/</sup><sup>-)</sup></i> Zebrafish Larvae. | Drepper C et al. | β | 2025 | β |
| Investigation of brain structures and potential mechanisms associated with ADHD: Insights from Mendelian randomization and genetic analysis. | Hu X et al. | β | 2025 | β |
| Neurodevelopment Is Dependent on Maternal Diet: Placenta and Brain Glucose Transporters GLUT1 and GLUT3. | Daida T et al. | β | 2024 | β |
| Systematic review of mitochondrial genetic variation in attention-deficit/hyperactivity disorder. | Giannoulis SV et al. | β | 2024 | β |
| Genetic architecture of ADHD and overlap with other psychiatric disorders and cognition-related phenotypes. | RibasΓ©s M et al. | β | 2023 | β |
| Shared Genetic Risk in the Association of Screen Time With Psychiatric Problems in Children. | Zhang Y et al. | β | 2023 | β |
| ADHD co-morbidities: A review of implication of gene Γ environment effects with dopamine-related genes. | Kanarik M et al. | β | 2022 | β |
| Mitochondrial Dysfunction in Attention Deficit Hyperactivity Disorder. | ΓΔΓΌtlΓΌ H et al. | β | 2022 | β |
| Mitochondrial protein dysfunction in pathogenesis of neurological diseases. | Wang L et al. | β | 2022 | β |
| Promising Developments in the Use of Induced Pluripotent Stem Cells in Research of ADHD. | Yde Ohki CM et al. | β | 2022 | β |
| Research models of neurodevelopmental disorders: The right model in the right place. | Damianidou E et al. | β | 2022 | β |
| SLC2A3 variants in familial and sporadic congenital heart diseases in a Chinese Yunnan population. | Ma L et al. | β | 2022 | β |
| Copy Number Variants and Polygenic Risk Scores Predict Need of Care in Autism and/or ADHD Families. | LaBianca S et al. | β | 2021 | β |
| Genetic Testing in Neurodevelopmental Disorders. | Savatt JM et al. | β | 2021 | β |
| Genetic variations influence brain changes in patients with attention-deficit hyperactivity disorder. | Yadav SK et al. | β | 2021 | β |
| Glucose transporter 3 in neuronal glucose metabolism: Health and diseases. | Peng W et al. | β | 2021 | β |
| Is there a special relationship between complex I activity and nigral neuronal loss in Parkinson's disease? A critical reappraisal. | Subrahmanian N et al. | β | 2021 | β |
| Neuropeptide Y Variation Is Associated With Altered Static and Dynamic Functional Connectivity of the Salience Network. | Warthen KG et al. | β | 2021 | β |
| Serotonin-specific neurons differentiated from human iPSCs form distinct subtypes with synaptic protein assembly. | Jansch C et al. | β | 2021 | β |
| Appropriateness of array-CGH in the ADHD clinics: A comparative study. | Baccarin M et al. | β | 2020 | β |
| Cellular effects and clinical implications of SLC2A3 copy number variation. | Ziegler GC et al. | β | 2020 | β |
| Development of the Korean Practice Parameter for Adult Attention-Deficit/Hyperactivity Disorder. | Bahn GH et al. | β | 2020 | β |
| From man to fly - convergent evidence links FBXO25 to ADHD and comorbid psychiatric phenotypes. | Harich B et al. | β | 2020 | β |
| Genetics of ADHD: What Should the Clinician Know? | Grimm O et al. | β | 2020 | β |
| Identification of ADHD risk genes in extended pedigrees by combining linkage analysis and whole-exome sequencing. | Corominas J et al. | β | 2020 | β |
| Mutations in sphingolipid metabolism genes are associated with ADHD. | Henriquez-Henriquez M et al. | β | 2020 | β |
| Cross-species models of attention-deficit/hyperactivity disorder and autism spectrum disorder: lessons from CNTNAP2, ADGRL3, and PARK2. | Dalla Vecchia E et al. | β | 2019 | β |
| Genetics of attention deficit hyperactivity disorder. | Faraone SV et al. | β | 2019 | β |
| Neuropeptide Y and representation of salience in human nucleus accumbens. | Warthen KG et al. | β | 2019 | β |
| Transcript Analysis of Zebrafish GLUT3 Genes, <i>slc2a3a</i> and <i>slc2a3b</i>, Define Overlapping as Well as Distinct Expression Domains in the Zebrafish (<i>Danio rerio</i>) Central Nervous System. | Lechermeier CG et al. | β | 2019 | β |
| Updated European Consensus Statement on diagnosis and treatment of adult ADHD. | Kooij JJS et al. | β | 2019 | β |
| Common and specific genes and peripheral biomarkers in children and adults with attention-deficit/hyperactivity disorder. | Bonvicini C et al. | β | 2018 | β |
| [Genetics and epigenetics of attention deficit hyperactivity disorder]. | Mustafin RN et al. | β | 2018 | β |
| Live fast, die young? A review on the developmental trajectories of ADHD across the lifespan. | Franke B et al. | β | 2018 | β |
| Neural Deletion of Glucose Transporter Isoform 3 Creates Distinct Postnatal and Adult Neurobehavioral Phenotypes. | Shin BC et al. | β | 2018 | β |
| Recent developments in the genetics of attention-deficit hyperactivity disorder. | Grimm O et al. | β | 2018 | β |
| Worms on the spectrum - C. elegans models in autism research. | Schmeisser K et al. | β | 2018 | β |
| Analysis of shared homozygosity regions in Saudi siblings with attention deficit hyperactivity disorder. | Shinwari JMA et al. | β | 2017 | β |
| An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry. | Meyers JL et al. | β | 2017 | β |
| Brain imaging genetics in ADHD and beyond - Mapping pathways from gene to disorder at different levels of complexity. | Klein M et al. | β | 2017 | β |
| Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants. | Serra-JuhΓ© C et al. | β | 2017 | β |
| Sex-Specific Life Course Changes in the Neuro-Metabolic Phenotype of Glut3 Null Heterozygous Mice: Ketogenic Diet Ameliorates Electroencephalographic Seizures and Improves Sociability. | Dai Y et al. | β | 2017 | β |
| SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder. | Merker S et al. | β | 2017 | β |
| An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder. | Lima Lde A et al. | β | 2016 | β |
| Genetics of attention-deficit/hyperactivity disorder: an update. | Akutagava-Martins GC et al. | β | 2016 | β |
| Improving treatment of neurodevelopmental disorders: recommendations based on preclinical studies. | Homberg JR et al. | β | 2016 | β |
| The domesticated brain: genetics of brain mass and brain structure in an avian species | Henriksen R et al. | β | 2016 | β |
| The domesticated brain: genetics of brain mass and brain structure in an avian species. | Henriksen R et al. | β | 2016 | β |
| Whole-Exome Sequencing Reveals Increased Burden ofΒ Rare Functional and Disruptive Variants in CandidateΒ Risk Genes in Individuals With Persistent Attention-Deficit/Hyperactivity Disorder. | Demontis D et al. | β | 2016 | β |
| A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients. | Schwarz R et al. | β | 2015 | β |
| Attention-deficit/hyperactivity disorder. | Faraone SV et al. | β | 2015 | β |
| Burden analysis of rare microdeletions suggests a strong impact of neurodevelopmental genes in genetic generalised epilepsies. | Lal D et al. | β | 2015 | β |
| Case-control genome-wide association study of persistent attention-deficit hyperactivity disorder identifies FBXO33 as a novel susceptibility gene for the disorder. | SΓ‘nchez-Mora C et al. | β | 2015 | β |
| Dopamine receptor DRD4 gene and stressful life events in persistent attention deficit hyperactivity disorder. | SΓ‘nchez-Mora C et al. | β | 2015 | β |
| Enhanced inhibitory control by neuropeptide Y Y5 receptor blockade in rats. | Bari A et al. | β | 2015 | β |
| The molecular genetic architecture of attention deficit hyperactivity disorder. | Hawi Z et al. | β | 2015 | β |
| Ultrastructural Correlates of Enhanced Norepinephrine and Neuropeptide Y Cotransmission in the Spontaneously Hypertensive Rat Brain. | Kourtesis I et al. | β | 2015 | β |
| An inherited small microdeletion at 15q13.3 in a patient with early-onset obsessive-compulsive disorder. | Cappi C et al. | β | 2014 | β |
| Applying imaging genetics to ADHD: the promises and the challenges. | Wu Z et al. | β | 2014 | β |
| Biomarkers in the diagnosis of ADHD--promising directions. | Faraone SV et al. | β | 2014 | β |
| Epilepsy associated with autism and attention deficit hyperactivity disorder: is there a genetic link? | Lo-Castro A et al. | β | 2014 | β |
| Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder. | Jarick I et al. | β | 2014 | β |
| Molecular genetic studies of ADHD and its candidate genes: a review. | Li Z et al. | β | 2014 | β |
| Pleckstrin homology domain containing 6 protein (PLEKHA6) polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients. | Spellmann I et al. | β | 2014 | β |
| Acetylcholine-metabolizing butyrylcholinesterase (BCHE) copy number and single nucleotide polymorphisms and their role in attention-deficit/hyperactivity syndrome. | Jacob CP et al. | β | 2013 | β |
| A computational method for detecting copy number variations using scale-space filtering. | Lee J et al. | β | 2013 | β |
| Development and automation of a test of impulse control in zebrafish. | Parker MO et al. | β | 2013 | β |
| Genetics of attention-deficit/hyperactivity disorder: current findings and future directions. | Akutagava-Martins GC et al. | β | 2013 | β |
| Haplotype co-segregation with attention deficit-hyperactivity disorder in unrelated German multi-generation families. | Lin MK et al. | β | 2013 | β |
| High loading of polygenic risk for ADHD in children with comorbid aggression. | Hamshere ML et al. | β | 2013 | β |
| Impact of the ADHD-susceptibility gene CDH13 on development and function of brain networks. | Rivero O et al. | β | 2013 | β |
| Neuropeptide Y and posttraumatic stress disorder. | Sah R et al. | β | 2013 | β |
| Nonhuman primate models in the genomic era: a paradigm shift. | Vallender EJ et al. | β | 2013 | β |
| The mitochondrial disease associated protein Ndufaf2 is dispensable for Complex-1 assembly but critical for the regulation of oxidative stress. | Schlehe JS et al. | β | 2013 | β |
| Toward developmental models of psychiatric disorders in zebrafish. | Norton WH | β | 2013 | β |
| What have we learnt about the causes of ADHD? | Thapar A et al. | β | 2013 | β |
| ADHD and autism: differential diagnosis or overlapping traits? A selective review. | Taurines R et al. | β | 2012 | β |
| ADHDgene: a genetic database for attention deficit hyperactivity disorder. | Zhang L et al. | β | 2012 | β |
| Attention-deficit/hyperactivity disorder genomics: update for clinicians. | Elia J et al. | β | 2012 | β |
| Behavioural genetics of childhood disorders. | Freitag CM et al. | β | 2012 | β |
| Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses. | Scassellati C et al. | β | 2012 | β |
| Genome-wide analysis of copy number variants in attention deficit hyperactivity disorder: the role of rare variants and duplications at 15q13.3. | Williams NM et al. | β | 2012 | β |
| Genome-wide survey of large rare copy number variants in Alzheimer's disease among Caribbean hispanics. | Ghani M et al. | β | 2012 | β |
| Genomic structural variation in psychiatric disorders. | Rucker JJ et al. | β | 2012 | β |
| Human-specific histone methylation signatures at transcription start sites in prefrontal neurons. | Shulha HP et al. | β | 2012 | β |
| Investigating the contribution of common genetic variants to the risk and pathogenesis of ADHD. | Stergiakouli E et al. | β | 2012 | β |
| Neurogenetics and Epigenetics in Impulsive Behaviour: Impact on Reward Circuitry. | Archer T et al. | β | 2012 | β |
| Pilot study on HTR2A promoter polymorphism, -1438G/A (rs6311) and a nearby copy number variation showed association with onset and severity in early onset obsessive-compulsive disorder. | Walitza S et al. | β | 2012 | β |
| Serotonin in the modulation of neural plasticity and networks: implications for neurodevelopmental disorders. | Lesch KP et al. | β | 2012 | β |
| Small rare recurrent deletions and reciprocal duplications in 2q21.1, including brain-specific ARHGEF4 and GPR148. | Dharmadhikari AV et al. | β | 2012 | β |
| The ADHD-susceptibility gene lphn3.1 modulates dopaminergic neuron formation and locomotor activity during zebrafish development. | Lange M et al. | β | 2012 | β |
| The genetics of attention deficit/hyperactivity disorder in adults, a review. | Franke B et al. | β | 2012 | β |
| The genetics of Tourette syndrome. | Deng H et al. | β | 2012 | β |
| Under diagnosis of adult ADHD: cultural influences and societal burden. | Asherson P et al. | β | 2012 | β |
| What causes attention deficit hyperactivity disorder? | Thapar A et al. | β | 2012 | β |
| What is complex about complex disorders? | Mitchell KJ | β | 2012 | β |
| X chromosome inactivation in women with alcoholism. | Manzardo AM et al. | β | 2012 | β |
| A genome-wide CNV association study on panic disorder in a Japanese population. | Kawamura Y et al. | β | 2011 | β |
| A lifetime of attention-deficit/hyperactivity disorder: diagnostic challenges, treatment and neurobiological mechanisms. | Geissler J et al. | β | 2011 | β |
| Clinical and cognitive characteristics of children with attention-deficit hyperactivity disorder, with and without copy number variants. | Langley K et al. | β | 2011 | β |
| DIRAS2 is associated with adult ADHD, related traits, and co-morbid disorders. | Reif A et al. | β | 2011 | β |
| Following the genes: a framework for animal modeling of psychiatric disorders. | Mitchell KJ et al. | β | 2011 | β |
| Genome arrays for the detection of copy number variations in idiopathic mental retardation, idiopathic generalized epilepsy and neuropsychiatric disorders: lessons for diagnostic workflow and research. | Hochstenbach R et al. | β | 2011 | β |
| Genome-wide association study in German patients with attention deficit/hyperactivity disorder. | Hinney A et al. | β | 2011 | β |
| Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder. | Elia J et al. | β | 2011 | β |
| Rare copy number variation discovery and cross-disorder comparisons identify risk genes for ADHD. | Lionel AC et al. | β | 2011 | β |
| Sex-dependent control of murine emotional-affective behaviour in health and colitis by peptide YY and neuropeptide Y. | Painsipp E et al. | β | 2011 | β |
| Developmental comorbidity in attention-deficit/hyperactivity disorder. | Taurines R et al. | β | 2010 | β |
| Fitting the pieces together: current research on the genetic basis of attention-deficit/hyperactivity disorder (ADHD). | Stergiakouli E et al. | β | 2010 | β |