TY - JOUR
T1 - Evaluation of common variants in 16 genes involved in the regulation of neurotransmitter release in ADHD
AU - Sánchez-Mora, Cristina
AU - Cormand, Bru
AU - Ramos-Quiroga, Josep Antoni
AU - Hervás, Amaia
AU - Bosch, Rosa
AU - Palomar, Glòria
AU - Nogueira, Mariana
AU - Gómez-Barros, Núria
AU - Richarte, Vanesa
AU - Corrales, Montse
AU - Garcia-Martinez, Iris
AU - Corominas, Roser
AU - Guijarro, Silvina
AU - Bigorra, Aitana
AU - Bayés, Mònica
AU - Casas, Miguel
AU - Ribasés, Marta
PY - 2013/6/1
Y1 - 2013/6/1
N2 - Attention-deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by inappropriate difficulties to sustain attention, control impulses and modulate activity level. Although ADHD is one of the most prevalent childhood psychiatric disorders, it also persists into adulthood in around 30-50% of the cases. Based on the effect of psychostimulants used in the pharmacological treatment of ADHD, dysfunctions in neuroplasticity mechanisms and synapses have been postulated to be involved in the pathophysiology of ADHD. With this background, we evaluated, both in childhood and adulthood ADHD, the role of several genes involved in the control of neurotransmitter release through synaptic vesicle docking, fusion and recycling processes by means of a population-based association study. We analyzed single nucleotide polymorphisms across 16 genes in a clinical sample of 950 ADHD patients (506 adults and 444 children) and 905 controls. Single and multiple-marker analyses identified several significant associations after correcting for multiple testing with a false discovery rate (FDR) of 15%: (i) the SYT2 gene was strongly associated with both adulthood and childhood ADHD (. p=0.001, OR=1.49 (1.18-1.89) and p=0.007, OR=1.37 (1.09-1.72), respectively) and (ii) STX1A was found associated with ADHD only in adults (. p=0.0041; OR=1.28 (1.08-1.51)). These data provide preliminary evidence for the involvement of genes that participate in the control of neurotransmitter release in the genetic predisposition to ADHD through a gene-system association study. Further follow-up studies in larger cohorts and deep-sequencing of the associated genomic regions are required to identify sequence variants directly involved in ADHD. © 2012 Elsevier B.V. and ECNP.
AB - Attention-deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by inappropriate difficulties to sustain attention, control impulses and modulate activity level. Although ADHD is one of the most prevalent childhood psychiatric disorders, it also persists into adulthood in around 30-50% of the cases. Based on the effect of psychostimulants used in the pharmacological treatment of ADHD, dysfunctions in neuroplasticity mechanisms and synapses have been postulated to be involved in the pathophysiology of ADHD. With this background, we evaluated, both in childhood and adulthood ADHD, the role of several genes involved in the control of neurotransmitter release through synaptic vesicle docking, fusion and recycling processes by means of a population-based association study. We analyzed single nucleotide polymorphisms across 16 genes in a clinical sample of 950 ADHD patients (506 adults and 444 children) and 905 controls. Single and multiple-marker analyses identified several significant associations after correcting for multiple testing with a false discovery rate (FDR) of 15%: (i) the SYT2 gene was strongly associated with both adulthood and childhood ADHD (. p=0.001, OR=1.49 (1.18-1.89) and p=0.007, OR=1.37 (1.09-1.72), respectively) and (ii) STX1A was found associated with ADHD only in adults (. p=0.0041; OR=1.28 (1.08-1.51)). These data provide preliminary evidence for the involvement of genes that participate in the control of neurotransmitter release in the genetic predisposition to ADHD through a gene-system association study. Further follow-up studies in larger cohorts and deep-sequencing of the associated genomic regions are required to identify sequence variants directly involved in ADHD. © 2012 Elsevier B.V. and ECNP.
KW - ADHD
KW - Attention-deficit hyperactivity disorder
KW - Case-control association study
KW - Neurotransmission
KW - SNARE complex
KW - STX1A
KW - Synaptic exocytosis
KW - SYT2
U2 - 10.1016/j.euroneuro.2012.07.014
DO - 10.1016/j.euroneuro.2012.07.014
M3 - Article
VL - 23
SP - 426
EP - 435
IS - 6
ER -