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PPP2R2C as a candidate gene of a temperament and character trait-based endophenotype of ADHD

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ADHD Attention Deficit and Hyperactivity Disorders

Abstract

There are several lines of evidence that the 4p16 region is a candidate locus of both attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder. None of the harbored candidate genes of this region were hitherto shown to be associated with ADHD despite promising functionality. One of the most promising candidate genes in this region is protein phosphatase 2, regulatory subunit B, gamma (PPP2R2C), which, however, thus far has not been assessed for a potential association with ADHD. A total of 513 in- and outpatients affected with adult ADHD and 536 controls as well as 170 nuclear families with 249 children affected with ADHD were genotyped for 35 SNPs, which tagged the promoter region, the 5′ and 3′ UTRs, and the exons of the PPP2R2C. Two independent samples provided evidence that the major G allele of rs16838844 increases risk toward ADHD. Allelic variations of PPP2R2C rs16838698 on the other hand might be associated with a variety of personality traits. There is evidence that allelic variation in PPP2R2C may be associated with a variety of personality traits and ADHD per se. Nevertheless, as all those conditions are comorbid, PPP2R2C might reflect a common underlying neurobiological risk factor.

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Acknowledgments

This study was supported by the DFG (Grant RE1632/1-1, /1-3 and /5 to AR, KFO 125 to AR, CPJ, AW, SW, HS and KPL; SFB 581 to KPL, SFB TRR 58 to AR and KPL; GR 1912/5-1, to HG), BMBF (01GV0605 to KPL), BMBF (IZKF Würzburg, 01KS9603, to KPL; IZKF N-27-N, to AR), and the EC (NEWMOOD LSHM-CT-2003-503474, to KPL).

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Authors and Affiliations

  1. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080, Wuerzburg, Germany

    Christian Jacob, Lena Weißflog, Martin Herrmann, Stefanie Liedel, Susanne Reichert, Silke Groß-Lesch, Klaus-Peter Lesch & Andreas Reif

  2. Institute of Medical Biometry and Epidemiology, University of Marburg, Marburg, Germany

    Thuy Tran Nguyen & Karin Zamzow

  3. Molecular Psychiatry Laboratory of Translational Neuroscience, ADHD Clinical Research Network, Wuerzburg, Germany

    Christian Jacob, Susanne Reichert, Klaus-Peter Lesch & Andreas Reif

  4. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany

    Thomas Jans, Tobias Renner & Susanne Reichert

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  1. Christian Jacob
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  2. Thuy Tran Nguyen
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  3. Lena Weißflog
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  4. Martin Herrmann
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  5. Stefanie Liedel
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  7. Thomas Jans
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  10. Silke Groß-Lesch
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  11. Klaus-Peter Lesch
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  12. Andreas Reif
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Correspondence to Christian Jacob.

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Jacob, C., Nguyen, T.T., Weißflog, L. et al. PPP2R2C as a candidate gene of a temperament and character trait-based endophenotype of ADHD. ADHD Atten Def Hyp Disord 4, 145–152 (2012). https://doi.org/10.1007/s12402-012-0080-8

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  • DOI: https://doi.org/10.1007/s12402-012-0080-8

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