TY  - JOUR
A1  - Jarick, Ivonne
A1  - Volckmar, Anna-Lena
A1  - Pütter, Carolin
A1  - Pechlivanis, Sonali
A1  - Nguyen, Trang T.
A1  - Dauvermann, Maria R.
A1  - Beck, Sebastian
A1  - Albayrak, Özgür
A1  - Scherag, Susann
A1  - Gilsbach, Susanne
A1  - Cichon, Sven
A1  - Hoffmann, Per
A1  - Degenhardt, Franziska
A1  - Nöthen, Markus Maria
A1  - Schreiber, Stefan
A1  - Wichmann, Heinz Erich
A1  - Jöckel, Karl-Heinz
A1  - Heinrich, Joachim
A1  - Tiesler, Carla Marie Thérèse
A1  - Faraone, Stephen V.
A1  - Walitza, Susanne
A1  - Sinzig, Judith
A1  - Freitag, Christine M.
A1  - Meyer, Jobst
A1  - Herpertz-Dahlmann, Beate
A1  - Lehmkuh, Gerd
A1  - Renner, Tobias J.
A1  - Warnke, Andreas
A1  - Romanos, Marcel
A1  - Lesch, Klaus-Peter J.
A1  - Reif, Andreas
A1  - Schimmelmann, Benno G.
A1  - Hebebrand, Johannes
A1  - Scherag, André
A1  - Hinney, Anke
T1  - Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder
T2  - Molecular psychiatry
N2  - Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.
KW  - ADHD
KW  - children
KW  - CNVs
KW  - GWAS
KW  - PARK2
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37256
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-372560
SN  - 1476-5578
SN  - 1359-4184
N1  - Copyright © 2014 Macmillan Publishers Limited This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
VL  - 19
IS  - 1
SP  - 115
EP  - 121
PB  - Macmillan
CY  - London
ER  -