A Population Based Study of the Genetic Association between Catecholamine Gene Variants and Spontaneous Low-Frequency Fluctuations in Reaction Time Bastiaansen

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 = 0.02) and 100% power to detect a small/medium effect size (f = 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. PLOS ONE | DOI:10.1371/journal.pone. 0126461 May 15, 2015 1 / 10 OPEN ACCESS Citation: Bastiaansen JA, Cummins TDR, Riese H, van Roon AM, Nolte IM, Oldehinkel AJ, et al. (2015) A Population Based Study of the Genetic Association between Catecholamine Gene Variants and Spontaneous Low-Frequency Fluctuations in Reaction Time. PLoS ONE 10(5): e0126461. doi:10.1371/journal.pone. 0126461 Academic Editor: Qiang WANG, Sichuan University, CHINA Received: December 4, 2014 Accepted: April 3, 2015 Published: May 15, 2015 Copyright: © 2015 Bastiaansen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are available in the manuscript and its supporting information files. Funding: This research is part of the TRacking Adolescents' Individual Lives Survey (TRAILS). Participating centers of TRAILS include various departments of the University Medical Center and University of Groningen, the Erasmus University Medical Center Rotterdam, the University of Utrecht, the Radboud Medical Center Nijmegen, and the Parnassia Bavo group, all in the Netherlands.