title: Genome-wide analysis of attention deficit hyperactivity disorder in Norway.
abstract: BACKGROUND
  Attention deficit hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric condition, but it has been difficult to identify genes underlying this disorder. This study aimed to explore genetics of ADHD in an ethnically homogeneous Norwegian population by means of a genome-wide association (GWA) analysis followed by examination of candidate loci.
  
  
  METHODS
  Participants were recruited through Norwegian medical and birth registries as well as the general population. Presence of ADHD was defined according to DSM-IV criteria. Genotyping was performed using Illumina Human OmniExpress-12v1 microarrays. Statistical analyses were divided into several steps: (1) genome-wide association in the form of logistic regression in PLINK and follow-up pathway analyses performed in DAPPLE and INRICH softwares, (2) SNP-heritability calculated using genome-wide complex trait analysis (GCTA) tool, (3) gene-based association tests carried out in JAG software, and (4) evaluation of previously reported genome-wide signals and candidate genes of ADHD.
  
  
  RESULTS
  In total, 1.358 individuals (478 cases and 880 controls) and 598.384 autosomal SNPs were subjected to GWA analysis. No single polymorphism reached genome-wide significance. The strongest signal was observed at rs9949006 in the ENSG00000263745 gene (OR=1.51, 95% CI 1.28-1.79, p=1.38E-06). Pathway analyses of the top SNPs implicated genes involved in the regulation of gene expression, cell adhesion and inflammation. Among previously identified ADHD candidate genes, prominent association signals were observed for SLC9A9 (rs1393072, OR=1.46, 95% CI = 1.21-1.77, p=9.95E-05) and TPH2 (rs17110690, OR = 1.38, 95% CI = 1.14-1.66, p=8.31E-04).
  
  
  CONCLUSIONS
  This study confirms the complexity and heterogeneity of ADHD etiology. Taken together with previous findings, our results point to a spectrum of biological mechanisms underlying the symptoms of ADHD, providing targets for further genetic exploration of this complex disorder.
authors: K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.
authors: Tetyana
authors: T
authors: Zayats
authors: NORMENT, K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors: Lavinia
authors: L
authors: Athanasiu
authors: NORMENT, K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors: Ida
authors: I
authors: Sonderby
authors: Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; NORMENT, K.G. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors: Srdjan
authors: S
authors: Djurovic
authors: NORMENT, K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
authors: Lars T
authors: LT
authors: Westlye
authors: Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University Of Oslo, Oslo, Norway.
authors: Christian K
authors: CK
authors: Tamnes
authors: Department of Neurology, Akershus University Hospital, Lørenskog, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
authors: Tormod
authors: T
authors: Fladby
authors: Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
authors: Heidi
authors: H
authors: Aase
authors: Oslo University Hospital, Child and Adolescent Mental Health Research Unit, Oslo, Norway.
authors: Pål
authors: P
authors: Zeiner
authors: Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
authors: Ted
authors: T
authors: Reichborn-Kjennerud
authors: K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Clinical Science, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors: Per M
authors: PM
authors: Knappskog
authors: Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
authors: Gun Peggy
authors: GP
authors: Knudsen
authors: NORMENT, K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors: Ole A
authors: OA
authors: Andreassen
authors: K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Clinical Science, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors: Stefan
authors: S
authors: Johansson
authors: K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
authors: Jan
authors: J
authors: Haavik
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics; D014365:Tryptophan Hydroxylase / Q000235:genetics
chemical_list: C478541:SLC9A9 protein, human; D017923:Sodium-Hydrogen Exchangers; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase