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, Christopher D. ORCID: https://orcid.org/0000-0001-6058-4114 and Bellgrove, M. A. 2014. Alpha-2A adrenergic receptor gene variants are associated with increased intra-individual variability in response time. Molecular Psychiatry 19 , pp. 1031-1036. 10.1038/mp.2013.140

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology
Subjects:	B Philosophy. Psychology. Religion > BF Psychology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	attention; dopamine; executive; genetics; ICV; noradrenaline.
Publisher:	Nature Publishing Group
ISSN:	1359-4184
Last Modified:	25 Oct 2022 08:22
URI:	https://orca.cardiff.ac.uk/id/eprint/52549

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