title: Alpha-2A adrenergic receptor gene variants are associated with increased intra-individual variability in response time.
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), p corrected=0.004, 0.012, respectively, whereas the selective attention variability factor was associated with a TH SNP (rs3842727), p corrected=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.
authors.affiliation: 1] School of Psychology, Monash University, Melbourne, VIC, Australia [2] Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: T D R
authors.initials: TD
authors.lastname: Cummins
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: O
authors.initials: O
authors.lastname: Jacoby
authors.affiliation: 1] School of Psychology, Monash University, Melbourne, VIC, Australia [2] Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Z
authors.initials: Z
authors.lastname: Hawi
authors.affiliation: 1] Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia [2] Prince Charles Hospital, Brisbane, QLD, Australia.
authors.forename: L S
authors.initials: LS
authors.lastname: Nandam
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: M A V
authors.initials: MA
authors.lastname: Byrne
authors.affiliation: 1] Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia [2] Department of Child and Adolescent Psychiatry, Seoul National University, Seoul, South Korea.
authors.forename: B-N
authors.initials: BN
authors.lastname: Kim
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Wagner
authors.affiliation: School of Psychology, Cardiff University, Cardiff, Wales, UK.
authors.forename: C D
authors.initials: CD
authors.lastname: Chambers
authors.affiliation: 1] School of Psychology, Monash University, Melbourne, VIC, Australia [2] Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia [3] School of Psychology, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Bellgrove
mesh_terms: D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000523:psychology; D001315:Australia; D005260:Female; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D006801:Humans; D007206:Individuality; D008297:Male; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D011569:Psychiatric Status Rating Scales; D011930:Reaction Time / Q000235:genetics*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C547768:ADRA2A protein, human; D018341:Receptors, Adrenergic, alpha-2; D014446:Tyrosine 3-Monooxygenase