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A Potential Role for the STXBP5-AS1 Gene in Adult ADHD Symptoms.
Arias-Vásquez, A; Groffen, A J; Spijker, S; Ouwens, K G; Klein, M; Vojinovic, D; Galesloot, T E; Bralten, J; Hottenga, J J; van der Most, P J; Kattenberg, V M; Pool, R; Nolte, I M; Penninx, B W J H; Fedko, I O; Dolan, C V; Nivard, M G; den Braber, A; van Duijn, C M; Hoekstra, P J; Buitelaar, J K; Kiemeney, L A; Hoogman, M; Middeldorp, C M; Draisma, H H M; Vermeulen, S H; Sánchez-Mora, C; Ramos-Quiroga, J A; Ribasés, M; Hartman, C A; Kooij, J J S; Amin, N; Smit, A B; Franke, B; Boomsma, D I.
Afiliación
  • Arias-Vásquez A; Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. Alejandro.AriasVasquez@radboudumc.nl.
  • Groffen AJ; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Route 855, Postbus 9101, 6500 HB, Nijmegen, The Netherlands. Alejandro.AriasVasquez@radboudumc.nl.
  • Spijker S; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. Alejandro.AriasVasquez@radboudumc.nl.
  • Ouwens KG; Department of Functional Genomics and Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam and VU Medical Center Amsterdam, Amsterdam, The Netherlands.
  • Klein M; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
  • Vojinovic D; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
  • Galesloot TE; Amsterdam Public Health, Amsterdam, The Netherlands.
  • Bralten J; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Route 855, Postbus 9101, 6500 HB, Nijmegen, The Netherlands.
  • Hottenga JJ; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • van der Most PJ; Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Kattenberg VM; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Route 855, Postbus 9101, 6500 HB, Nijmegen, The Netherlands.
  • Pool R; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
  • Nolte IM; Amsterdam Public Health, Amsterdam, The Netherlands.
  • Penninx BWJH; Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Fedko IO; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
  • Dolan CV; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
  • Nivard MG; Amsterdam Public Health, Amsterdam, The Netherlands.
  • den Braber A; Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • van Duijn CM; Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
  • Hoekstra PJ; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
  • Buitelaar JK; Amsterdam Public Health, Amsterdam, The Netherlands.
  • Kiemeney LA; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
  • Hoogman M; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
  • Middeldorp CM; Amsterdam Public Health, Amsterdam, The Netherlands.
  • Draisma HHM; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
  • Vermeulen SH; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Sánchez-Mora C; Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Ramos-Quiroga JA; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Ribasés M; Karakter, Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
  • Hartman CA; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Route 855, Postbus 9101, 6500 HB, Nijmegen, The Netherlands.
  • Kooij JJS; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
  • Amin N; Child Health Research Centre, University of Queensland, Brisbane, Australia.
  • Smit AB; Child and Youth Mental Health Service, Children's Health Queensland Hospital and Health Services, Brisbane, Australia.
  • Franke B; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
  • Boomsma DI; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Behav Genet ; 49(3): 270-285, 2019 05.
Article en En | MEDLINE | ID: mdl-30659475
We aimed to detect Attention-deficit/hyperactivity (ADHD) risk-conferring genes in adults. In children, ADHD is characterized by age-inappropriate levels of inattention and/or hyperactivity-impulsivity and may persists into adulthood. Childhood and adulthood ADHD are heritable, and are thought to represent the clinical extreme of a continuous distribution of ADHD symptoms in the general population. We aimed to leverage the power of studies of quantitative ADHD symptoms in adults who were genotyped. Within the SAGA (Study of ADHD trait genetics in adults) consortium, we estimated the single nucleotide polymorphism (SNP)-based heritability of quantitative self-reported ADHD symptoms and carried out a genome-wide association meta-analysis in nine adult population-based and case-only cohorts of adults. A total of n = 14,689 individuals were included. In two of the SAGA cohorts we found a significant SNP-based heritability for self-rated ADHD symptom scores of respectively 15% (n = 3656) and 30% (n = 1841). The top hit of the genome-wide meta-analysis (SNP rs12661753; p-value = 3.02 × 10-7) was present in the long non-coding RNA gene STXBP5-AS1. This association was also observed in a meta-analysis of childhood ADHD symptom scores in eight population-based pediatric cohorts from the Early Genetics and Lifecourse Epidemiology (EAGLE) ADHD consortium (n = 14,776). Genome-wide meta-analysis of the SAGA and EAGLE data (n = 29,465) increased the strength of the association with the SNP rs12661753. In human HEK293 cells, expression of STXBP5-AS1 enhanced the expression of a reporter construct of STXBP5, a gene known to be involved in "SNAP" (Soluble NSF attachment protein) Receptor" (SNARE) complex formation. In mouse strains featuring different levels of impulsivity, transcript levels in the prefrontal cortex of the mouse ortholog Gm28905 strongly correlated negatively with motor impulsivity as measured in the five choice serial reaction time task (r2 = - 0.61; p = 0.004). Our results are consistent with an effect of the STXBP5-AS1 gene on ADHD symptom scores distribution and point to a possible biological mechanism, other than antisense RNA inhibition, involved in ADHD-related impulsivity levels.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Trastorno por Déficit de Atención con Hiperactividad / Proteínas R-SNARE / ARN Largo no Codificante / Proteínas del Tejido Nervioso Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies / Systematic_reviews Límite: Adult / Animals / Female / Humans / Male Idioma: En Revista: Behav Genet Año: 2019 Tipo del documento: Article País de afiliación: Países Bajos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Trastorno por Déficit de Atención con Hiperactividad / Proteínas R-SNARE / ARN Largo no Codificante / Proteínas del Tejido Nervioso Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies / Systematic_reviews Límite: Adult / Animals / Female / Humans / Male Idioma: En Revista: Behav Genet Año: 2019 Tipo del documento: Article País de afiliación: Países Bajos