title: Evaluation of common variants in 16 genes involved in the regulation of neurotransmitter release in ADHD.
abstract: 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.
authors.affiliation: Psychiatric Genetics Unit, Institut de Recerca Vall d'Hebron (VHIR), Barcelona, Catalonia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez-Mora
authors.forename: Bru
authors.initials: B
authors.lastname: Cormand
authors.forename: Josep Antoni
authors.initials: JA
authors.lastname: Ramos-Quiroga
authors.forename: Amaia
authors.initials: A
authors.lastname: Hervás
authors.forename: Rosa
authors.initials: R
authors.lastname: Bosch
authors.forename: Glòria
authors.initials: G
authors.lastname: Palomar
authors.forename: Mariana
authors.initials: M
authors.lastname: Nogueira
authors.forename: Núria
authors.initials: N
authors.lastname: Gómez-Barros
authors.forename: Vanesa
authors.initials: V
authors.lastname: Richarte
authors.forename: Montse
authors.initials: M
authors.lastname: Corrales
authors.forename: Iris
authors.initials: I
authors.lastname: Garcia-Martinez
authors.forename: Roser
authors.initials: R
authors.lastname: Corominas
authors.forename: Silvina
authors.initials: S
authors.lastname: Guijarro
authors.forename: Aitana
authors.initials: A
authors.lastname: Bigorra
authors.forename: Mònica
authors.initials: M
authors.lastname: Bayés
authors.forename: Miguel
authors.initials: M
authors.lastname: Casas
authors.forename: Marta
authors.initials: M
authors.lastname: Ribasés
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D013030:Spain; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism; D055815:Young Adult
chemical_list: D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents