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

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics - Tập 159B Số 2 - Trang 131-140 - 2012
Alexis C. Wood1,2, Janita Bralten3,4,2, Alejandro Arias Vásquez4,5, Marjolein Luman6, Jaap Ooterlaan6, Joseph A. Sergeant6, Stephen V. Faraone7, Jan K. Buitelaar3,8, Barbara Franke4,5, Jonna Kuntsi9, Nanda Rommelse5,8
1Department of Epidemiology and Section on Statistical Genetics, University of Alabama at Birmingham, School of Public Health, Birmingham, Alabama
2Frazier-Wood and Bralten are joint 1st authors. They contributed equally.
3Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
4Department of Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
5Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
6Department of Clinical Neuropsychology, VU University Amsterdam, The Netherlands
7Departments of Psychiatry and Neuroscience and Physiology, SUNY Upstate Medical University, New York
8Karakter, Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands
9King's College London, MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, London, United Kingdom

Tóm tắt

AbstractAttention‐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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American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Tập 159B Số 2

131-140

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