Alpha-2A adrenergic receptor gene variants are associated with increased intra-individual variability in response time

Cummins, T. D. R., Jacoby, O., Hawi. Z., Nandam, L. S., Byrne, M. A. V., Kim, B.-N., Wagner, J., Chambers, C. D. and Bellgrove. M A. (2013) Alpha-2A adrenergic receptor gene variants are associated with increased intra-individual variability in response time. Molecular Psychiatry, 19 9: 1031-1036. doi:10.1038/mp.2013.140


Author Cummins, T. D. R.
Jacoby, O.
Hawi. Z.
Nandam, L. S.
Byrne, M. A. V.
Kim, B.-N.
Wagner, J.
Chambers, C. D.
Bellgrove. M A.
Title Alpha-2A adrenergic receptor gene variants are associated with increased intra-individual variability in response time
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1359-4184
1476-5578
Publication date 2013-10-29
Year available 2013
Sub-type Article (original research)
DOI 10.1038/mp.2013.140
Volume 19
Issue 9
Start page 1031
End page 1036
Total pages 6
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract Intra-individual variability in response time has been proposed as an important endophenotype for attention deficit hyperactivity disorder (ADHD). Here we asked whether intra-individual variability is predicted by common variation in catecholamine genes and whether it mediates the relationship between these gene variants and self-reported ADHD symptoms. A total of 402 non-clinical Australian adults of European descent completed a battery of five cognitive tasks and the Conners’ Adult ADHD Rating Scale. Exclusion criteria included the presence of major psychiatric or neurologic illnesses and substance dependency. A total of 21 subjects were excluded due to incomplete data or poor quality cognitive or genotyping data. The final sample comprised 381 subjects (201 males; mean age=21.2 years, s.d.=5.1 years). Principal components analysis on variability measures yielded two factors (response selection variability vs selective attention variability). Association of these factors with catecholamine gene variants was tested using single-step linear regressions, with multiple comparisons controlled using permutation analysis. The response selection variability factor was associated with two ADRA2A single-nucleotide polymorphisms (SNPs) (rs1800544, rs602618), pcorrected=0.004, 0.012, respectively, whereas the selective attention variability factor was associated with a TH SNP (rs3842727), pcorrected=0.024. A bootstrapping analysis indicated that the response selection variability factor mediated the relationship between the ADRA2A SNP rs1800544 and self-reported ADHD symptoms. Thus this study finds evidence that DNA variation in the ADRA2A gene may be causally related to ADHD-like behaviors, in part through its influence on intra-individual variability. Evidence was also found for a novel association between a TH gene variant and intra-individual variability.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print: 29 October 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
School of Medicine Publications
School of Psychology Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 27 Mar 2014, 23:37:09 EST by Debra McMurtrie on behalf of Queensland Brain Institute