Neuropsychological intra‐individual variability explains unique genetic variance of ADHD and shows suggestive linkage to chromosomes 12, 13, and 17
Open accessAbstract
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Response variability is regarded as a robust and well-replicated cognitive characteristic of DSM-defined ADHD.
“Increased response variability is considered to be one of the most robust and best replicated cognitive features of ADHD as defined by the DSM nomenclature.[42][43][44]”
Cites
Willcutt, E. G., Doyle, A. E., Nigg, J. T., Faraone, S. V., & Pennington, B. F. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.02.006 · Cited by 3,568 · see citing works
Self-citationThe structural basis of inter-individual differences in human behaviour and cognition
Kanai, R., & Rees, G. (2011) · Nature reviews. Neuroscience · doi:10.1038/nrn3000 · Cited by 1,055 · see citing works
Sonuga-Barke, E. J. S., & Castellanos, F. X. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.02.005 · Cited by 890 · see citing works
Sergeant, J. A. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.09.010 · Cited by 589 · see citing works
Self-citationVarieties of Attention-Deficit/Hyperactivity Disorder-Related Intra-Individual Variability
Castellanos, F. X., Sonuga-Barke, E. J. S., Scheres, A., Di Martino, A., Hyde, C., & Walters, J. R. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.12.005 · Cited by 540 · see citing works
Brookes, K., Xu, X., Chen, W., Zhou, K., Neale, B., Lowe, N., Aneey, R., Franke, B., Gill, M., Ebstein, R., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001869 · Cited by 533 · see citing works
Self-citationHalperin, J. M., Trampush, J. W., Miller, C. J., Marks, D. J., & Newcorn, J. H. (2008) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2008.01926.x · Cited by 252 · see citing works
Vaurio, R. G., Simmonds, D. J., & Mostofsky, S. H. (2009) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2009.01.022 · Cited by 240 · see citing works
Bidwell, L. C., Willcutt, E. G., DeFries, J. C., & Pennington, B. F. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.04.003 · Cited by 183 · see citing works
Kuntsi, J., Wood, A. C., Johnson, K. A., Andreou, P., Arias-Vasquez, A., Buitelaar, J. K., Rommelse, N. N. J., Sergeant, J. A., Sonuga-Barke, E. J., Uebel, H., et al. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.139 · Cited by 162 · see citing works
Self-citationRommelse, N. N. J., Arias-Vásquez, A., Altink, M. E., Buschgens, C. J. M., Fliers, E., Asherson, P., Faraone, S. V., Buitelaar, J. K., Sergeant, J. A., Oosterlaan, J., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.06.006 · Cited by 75 · see citing works
Neuropsychological measures probably facilitate heritability research of ADHD
ROMMELSE, N., ALTINK, M., MARTIN, N., BUSCHGENS, C., BUITELAAR, J., SERGEANT, J., & OOSTERLAAN, J. (2008) · Archives of Clinical Neuropsychology · doi:10.1016/j.acn.2008.06.002 · Cited by 42 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Live fast, die young? A review on the developmental trajectories of ADHD across the lifespan
Franke, B., Michelini, G., Asherson, P., Banaschewski, T., Bilbow, A., Buitelaar, J. K., Cormand, B., Faraone, S. V., Ginsberg, Y., Haavik, J., et al. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.08.001 · Cited by 643 · see citing works
Self-citationvan der Meer, J. M. J., Oerlemans, A. M., van Steijn, D. J., Lappenschaar, M. G. A., de Sonneville, L. M. J., Buitelaar, J. K., & Rommelse, N. N. J. (2012) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2012.08.024 · Cited by 303 · see citing works
Self-citationResponse inhibition and ADHD traits: Correlates and heritability in a community sample
Crosbie, J., Arnold, P., Paterson, A., Swanson, J., Dupuis, A., Li, X., Shan, J., Goodale, T., Tam, C., Strug, L. J., et al. (2013) · Journal of Abnormal Child Psychology · doi:10.1007/s10802-012-9693-9 · Cited by 218 · see citing works
Cognitive and neurophysiological markers of ADHD persistence and remission
Cheung, C. H. M., Rijsdijk, F., McLoughlin, G., Brandeis, D., Banaschewski, T., Asherson, P., & Kuntsi, J. (2016) · British Journal of Psychiatry · doi:10.1192/bjp.bp.114.145185 · Cited by 146 · see citing works
Self-citationWolfers, T., Onnink, A. M. H., Zwiers, M. P., Arias-Vasquez, A., Hoogman, M., Mostert, J. C., Kan, C. C., Slaats-Willemse, D., Buitelaar, J. K., & Franke, B. (2015) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.140154 · Cited by 52 · see citing works
Self-citationMichelini, G., Cheung, C. H. M., Kitsune, V., Brandeis, D., Banaschewski, T., McLoughlin, G., Asherson, P., Rijsdijk, F., & Kuntsi, J. (2021) · Journal of Attention Disorders · doi:10.1177/1087054718771191 · Cited by 27 · see citing works
Self-citationThissen, A. J. A. M., Luman, M., Hartman, C., Hoekstra, P., van Lieshout, M., Franke, B., Oosterlaan, J., Rommelse, N. N. J., & Buitelaar, J. K. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2014.05.015 · Cited by 22 · see citing works
Self-citationRommelse, N., Luman, M., & Kievit, R. (2020) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-020-01639-9 · Cited by 19 · see citing works
Self-citationPinto, R., Asherson, P., Ilott, N., Cheung, C. H. M., & Kuntsi, J. (2016) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32463 · Cited by 19 · see citing works
Self-citation
- Authors
- Frazier‐Wood, A. C., Bralten, J., Arias‐Vasquez, A., Luman, M., Ooterlaan, J., Sergeant, J., Faraone, S. V., Buitelaar, J., Franke, B., Kuntsi, J., & Rommelse, N. N. J.
- Affiliations
- Radboud University Medical Center (NL)
- Vrije Universiteit Amsterdam (NL)
- SUNY Upstate Medical University (US)
- Radboud University Nijmegen (NL)
- King's College London (GB)
- Corresponding author
- Rommelse, Nanda N. J.
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2012-01-05
- Volume
- 159B
- Issue
- 2
- Pages
- 131-140
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W2115861555
- Cited by
- 42
- References
- 12
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 4 · 2018: 6 · 2016: 3 · 2015: 9 · 2014: 4 · 2013: 6 · 2012: 2
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- SUNY Digital Repository Support (State University of New York System) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Mental Health (R01MH062873, R01 MH62873-01A1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, within-person variability, genetic linkage, chromosome 17p13.3, heritability
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Child, Chromosome Mapping, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 17, Female, Humans, Inhibition, Psychological, Intelligence, Genetic Linkage, Male, Memory, Short-Term, Neuropsychological Tests, Phenotype, Prognosis, Reading, Genetic Variation, Genome, Human, Case-Control Studies, Siblings
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
