Universität zu Köln

Jarick, I., Volckmar, A-L, Puetter, C., Pechlivanis, S., Nguyen, T. T., Dauvermann, M. R., Beck, S., Albayrak, Oe, Scherag, S., Gilsbach, S., Cichon, S., Hoffmann, P., Degenhardt, F., Noethen, M. M., Schreiber, S., Wichmann, H-E, Joeckel, K-H, Heinrich, J., Tiesler, C. M. T., Faraone, S. V., Walitza, S., Sinzig, J., Freitag, C., Meyer, J., Herpertz-Dahlmann, B., Lehmkuhl, G., Renner, T. J., Warnke, A., Romanos, M., Lesch, K-P, Reif, A., Schimmelmann, B. G., Hebebrand, J., Scherag, A. and Hinney, A. (2014). Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder. Mol. Psychiatr., 19 (1). S. 115 - 122. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5578

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Abstract

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 (> 500kb) 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 x 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 x 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 x 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Jarick, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Volckmar, A-L UNSPECIFIED UNSPECIFIED UNSPECIFIED Puetter, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pechlivanis, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nguyen, T. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dauvermann, M. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beck, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Albayrak, Oe UNSPECIFIED UNSPECIFIED UNSPECIFIED Scherag, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gilsbach, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cichon, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Degenhardt, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Noethen, M. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schreiber, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wichmann, H-E UNSPECIFIED UNSPECIFIED UNSPECIFIED Joeckel, K-H UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinrich, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tiesler, C. M. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Faraone, S. V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Walitza, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sinzig, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Freitag, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herpertz-Dahlmann, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmkuhl, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Renner, T. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Warnke, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Romanos, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lesch, K-P UNSPECIFIED UNSPECIFIED UNSPECIFIED Reif, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schimmelmann, B. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hebebrand, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scherag, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hinney, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-452533
DOI:	10.1038/mp.2012.161
Journal or Publication Title:	Mol. Psychiatr.
Volume:	19
Number:	1
Page Range:	S. 115 - 122
Date:	2014
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-5578
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DEFICIT HYPERACTIVITY DISORDER; RECURRENT MICRODELETIONS; MOLECULAR-GENETICS; ADHD; ASSOCIATION; VARIANTS; DISEASE; SCHIZOPHRENIA; DUPLICATIONS; AUTISM Multiple languages Biochemistry & Molecular Biology; Neurosciences; Psychiatry Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45253