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Neuropsychological intra-individual variability explains unique genetic variance of ADHD and shows suggestive linkage to chromosomes 12, 13, and 17

Authors

  • Alexis C. Frazier-Wood,

    1. Department of Epidemiology and Section on Statistical Genetics, University of Alabama at Birmingham, School of Public Health, Birmingham, Alabama
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    • Frazier-Wood and Bralten are joint 1st authors. They contributed equally.

  • Janita Bralten,

    1. Department of Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    2. Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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    • Frazier-Wood and Bralten are joint 1st authors. They contributed equally.

  • Alejandro Arias-Vasquez,

    1. Department of Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    2. Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Marjolein Luman,

    1. Department of Clinical Neuropsychology, VU University, Amsterdam, The Netherlands
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  • Jaap Ooterlaan,

    1. Department of Clinical Neuropsychology, VU University, Amsterdam, The Netherlands
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  • Joseph Sergeant,

    1. Department of Clinical Neuropsychology, VU University, Amsterdam, The Netherlands
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  • Stephen V. Faraone,

    1. Departments of Psychiatry and Neuroscience and Physiology, SUNY Upstate Medical University, New York
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  • Jan Buitelaar,

    1. Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    2. Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands
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  • Barbara Franke,

    1. Department of Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    2. Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Jonna Kuntsi,

    1. King's College London, MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, London, United Kingdom
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  • Nanda N. J. Rommelse

    Corresponding author
    1. Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    2. Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands
    • UMC Radboud, Reinier Postlaan 12, 6525 GC Nijmegen, The Netherlands.
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Errata

This article is corrected by:

  1. Errata: Erratum: Neuropsychological intra-individual variability explains unique genetic variance of adhd and shows suggestive linkage to chromosomes 12, 13, and 17 Volume 159B, Issue 3, 359, Article first published online: 15 February 2012

  • Conflict of interest: None.

  • How to Cite this Article: Frazier-Wood AC, Bralten J, Arias-Vasquez A, Luman M, Ooterlaan J, Sergeant J, Faraone SV, Buitelaar J, Franke B, Kuntsi J, Rommelse NNJ. 2012. Neuropsychological intra-individual variability explains unique genetic variance of ADHD and shows suggestive linkage to chromosomes 12, 13, and 17. Am J Med Genet Part B 159B:131–140.

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric disorder that is usually accompanied by neuropsychological impairments. The use of heritable, psychometrically robust traits that show association with the disorder of interest can increase the power of gene-finding studies. Due to the robust association of intra-individual variability with ADHD on a phenotypic and genetic level, intra-individual variability is a prime candidate for such an attempt. We aimed to combine intra-individual variability measures across tasks into one more heritable measure, to examine the relatedness to other cognitive factors, and to explore the genetic underpinnings through quantitative trait linkage analysis. Intra-individual variability measures from seven tasks were available for 238 ADHD families (350 ADHD-affected and 195 non-affected children) and 147 control families (271 children). Intra-individual variability measures from seven different tasks shared common variance and could be used to construct an aggregated measure. This aggregated measure was largely independent from other cognitive factors related to ADHD and showed suggestive linkage to chromosomes 12q24.3 (LOD = 2.93), 13q22.2 (LOD = 2.36), and 17p13.3 (LOD = 2.00). A common intra-individual variability construct can be extracted from very diverse neuropsychological tasks; this construct taps into unique genetic aspects of ADHD and may relate to loci conferring risk for ADHD (12q24.3 and 17p13.3) and possibly autism (12q24.3). Given that joining of data across sites boosts the power for genetic analyses, our findings are promising in showing that intra-individual variability measures are viable candidates for across site analyses where different tasks have been used. © 2012 Wiley Periodicals, Inc.

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