title: The role of ASTN2 variants in childhood and adult ADHD, comorbid disorders and associated personality traits.
abstract: Previous linkage and genome wide association (GWA) studies in ADHD indicated astrotactin 2 (ASTN2) as a candidate gene for attention-deficit/hyperactivity disorder (ADHD). ASTN2 plays a key role in glial-guided neuronal migration. To investigate whether common variants in ASTN2 contribute to ADHD disorder risk, we tested 63 SNPs spanning ASTN2 for association with ADHD and specific comorbid disorders in two samples: 171 families of children with ADHD and their parents (N = 592), and an adult sample comprising 604 adult ADHD cases and 974 controls. The C-allele of rs12376789 in ASTN2 nominally increased the risk for ADHD in the trio sample (p = 0.025). This was not observed in the adult case-control sample alone, but retained in the combined sample (nominal p = 0.030). Several other SNPs showed nominally significant association with comorbid disorders, especially anxiety disorder, in the childhood and adult ADHD samples. Some ASTN2 variants were nominally associated with personality traits in the adult ADHD sample and overlapped with risk alleles for comorbid disorders in childhood. None of the findings survived correction for multiple testing, thus, results do not support a major role of common variants in ASTN2 in the pathogenesis of ADHD, its comorbid disorders or ADHD associated personality traits.
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe University, Deutschordenstrasse 50, 60528, Frankfurt am Main, Germany. c.freitag@em.uni-frankfurt.de.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Freitag
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe University, Deutschordenstrasse 50, 60528, Frankfurt am Main, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lempp
authors.affiliation: Institute of Medical Biometry and Epidemiology, University of Marburg, Marburg, Germany.
authors.forename: T Trang
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Jacob
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.|Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Weissflog
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Romanos
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.|Department of Child and Adolescent Psychiatry, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Renner
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.|Department of Child and Adolescent Psychiatry and Psychotherapy, University of Zurich, Zurich, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Walitza
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Warnke
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Munich, Munich, Germany.|Department of Psychiatry and Psychotherapy, University of Halle, Halle, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.|Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010290:Parents / Q000523:psychology; D010551:Personality; D010554:Personality Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: C000593289:ASTN2 protein, human; D006023:Glycoproteins; D009419:Nerve Tissue Proteins
keywords: Anxiety disorder; Astrotactin 2; Attention-deficit/hyperactivity disorder; Comorbid disorders; Personality traits