title: A Population Based Study of the Genetic Association between Catecholamine Gene Variants and Spontaneous Low-Frequency Fluctuations in Reaction Time.
abstract: The catecholamines dopamine and noradrenaline have been implicated in spontaneous low-frequency fluctuations in reaction time, which are associated with attention deficit hyperactivity disorder (ADHD) and subclinical attentional problems. The molecular genetic substrates of these behavioral phenotypes, which reflect frequency ranges of intrinsic neuronal oscillations (Slow-4: 0.027-0.073 Hz; Slow-5: 0.010-0.027 Hz), have not yet been investigated. In this study, we performed regression analyses with an additive model to examine associations between low-frequency fluctuations in reaction time during a sustained attention task and genetic markers across 23 autosomal catecholamine genes in a large young adult population cohort (n = 964), which yielded greater than 80% power to detect a small effect size (f(2) = 0.02) and 100% power to detect a small/medium effect size (f(2) = 0.15). At significance levels corrected for multiple comparisons, none of the gene variants were associated with the magnitude of low-frequency fluctuations. Given the study's strong statistical power and dense coverage of the catecholamine genes, this either indicates that associations between low-frequency fluctuation measures and catecholamine gene variants are absent or that they are of very small effect size. Nominally significant associations were observed between variations in the alpha-2A adrenergic receptor gene (ADRA2A) and the Slow-5 band. This is in line with previous reports of an association between ADRA2A gene variants and general reaction time variability during response selection tasks, but the specific association of these gene variants and low-frequency fluctuations requires further confirmation. Pharmacological challenge studies could in the future provide convergent evidence for the noradrenergic modulation of both general and time sensitive measures of intra-individual variability in reaction time.
authors.affiliation: Interdisciplinary Center Psychopathology and Emotion regulation, Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jojanneke A
authors.initials: JA
authors.lastname: Bastiaansen
authors.affiliation: School of Psychological Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Tarrant D R
authors.initials: TD
authors.lastname: Cummins
authors.affiliation: Interdisciplinary Center Psychopathology and Emotion regulation, Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Harriëtte
authors.initials: H
authors.lastname: Riese
authors.affiliation: Department of Vascular Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Arie M
authors.initials: AM
authors.lastname: van Roon
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Ilja M
authors.initials: IM
authors.lastname: Nolte
authors.affiliation: Interdisciplinary Center Psychopathology and Emotion regulation, Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Albertine J
authors.initials: AJ
authors.lastname: Oldehinkel
authors.affiliation: School of Psychological Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Bellgrove
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics / Q000503:physiopathology; D002394:Catechol O-Methyltransferase / Q000235:genetics; D002395:Catecholamines / Q000235:genetics*; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D011930:Reaction Time / Q000235:genetics* / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics; D055815:Young Adult
chemical_list: C547768:ADRA2A protein, human; D002395:Catecholamines; D018341:Receptors, Adrenergic, alpha-2; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase