title: Time to wake up: No impact of COMT Val158Met gene variation on circadian preferences, arousal regulation and sleep.
abstract: Dopamine has been implicated in the regulation of sleep-wake states and the circadian rhythm. However, there is no consensus on the impact of two established dopaminergic gene variants: the catechol-O-methyltransferase Val158Met (COMT Val158Met; rs4680) and the dopamine D4 receptor Exon III variable-number-of-tandem-repeat polymorphism (DRD4 VNTR). Pursuing a multi-method approach, we examined their potential effects on circadian preferences, arousal regulation and sleep. Subjects underwent a 7-day actigraphy assessment (SenseWear Pro3), a 20-minute resting EEG (analyzed using VIGALL 2.0) and a body mass index (BMI) assessment. Further, they completed the Morningness-Eveningness Questionnaire (MEQ), the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). The sample comprised 4625 subjects (19-82 years) genotyped for COMT Val158Met, and 689 elderly subjects (64-82 years) genotyped for DRD4 VNTR. The number of subjects varied across phenotypes. Power calculations revealed a minimum required phenotypic variance explained by genotype ranging between 0.5% and 1.5% for COMT Val158Met and between 3.3% and 6.0% for DRD4 VNTR. Analyses did not reveal significant genotype effects on MEQ, ESS, PSQI, BMI, actigraphy and EEG variables. Additionally, we found no compelling evidence in sex- and age-stratified subsamples. Few associations surpassed the threshold of nominal significance (p < .05), providing some indication for a link between DRD4 VNTR and daytime sleepiness. Taken together, in light of the statistical power obtained in the present study, our data particularly suggest no impact of the COMT Val158Met polymorphism on circadian preferences, arousal regulation and sleep. The suggestive link between DRD4 VNTR and daytime sleepiness, on the other hand, might be worth investigation in a sample enriched with younger adults.
authors.affiliation: a LIFE - Leipzig Research Center for Civilization Diseases , University of Leipzig , Leipzig , Germany.|b Department of Psychiatry and Psychotherapy , University of Leipzig , Leipzig , Germany.|c Depression Research Center of the German Depression Foundation , Leipzig , Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Jawinski
authors.affiliation: b Department of Psychiatry and Psychotherapy , University of Leipzig , Leipzig , Germany.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tegelkamp
authors.affiliation: a LIFE - Leipzig Research Center for Civilization Diseases , University of Leipzig , Leipzig , Germany.|b Department of Psychiatry and Psychotherapy , University of Leipzig , Leipzig , Germany.|c Depression Research Center of the German Depression Foundation , Leipzig , Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sander
authors.affiliation: a LIFE - Leipzig Research Center for Civilization Diseases , University of Leipzig , Leipzig , Germany.|d Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics , University Hospital Leipzig , Leipzig , Germany.
authors.forename: Madlen
authors.initials: M
authors.lastname: Häntzsch
authors.affiliation: b Department of Psychiatry and Psychotherapy , University of Leipzig , Leipzig , Germany.
authors.forename: Jue
authors.initials: J
authors.lastname: Huang
authors.affiliation: a LIFE - Leipzig Research Center for Civilization Diseases , University of Leipzig , Leipzig , Germany.|b Department of Psychiatry and Psychotherapy , University of Leipzig , Leipzig , Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mauche
authors.affiliation: a LIFE - Leipzig Research Center for Civilization Diseases , University of Leipzig , Leipzig , Germany.|e Institute for Medical Informatics, Statistics and Epidemiology , University of Leipzig , Leipzig , Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Scholz
authors.affiliation: b Department of Psychiatry and Psychotherapy , University of Leipzig , Leipzig , Germany.|c Depression Research Center of the German Depression Foundation , Leipzig , Germany.
authors.forename: Janek
authors.initials: J
authors.lastname: Spada
authors.affiliation: a LIFE - Leipzig Research Center for Civilization Diseases , University of Leipzig , Leipzig , Germany.|c Depression Research Center of the German Depression Foundation , Leipzig , Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Ulke
authors.affiliation: a LIFE - Leipzig Research Center for Civilization Diseases , University of Leipzig , Leipzig , Germany.|d Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics , University Hospital Leipzig , Leipzig , Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Burkhardt
authors.affiliation: f Department of Psychiatry , Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt , Frankfurt , Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.affiliation: a LIFE - Leipzig Research Center for Civilization Diseases , University of Leipzig , Leipzig , Germany.|b Department of Psychiatry and Psychotherapy , University of Leipzig , Leipzig , Germany.|c Depression Research Center of the German Depression Foundation , Leipzig , Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hegerl
authors.affiliation: a LIFE - Leipzig Research Center for Civilization Diseases , University of Leipzig , Leipzig , Germany.|b Department of Psychiatry and Psychotherapy , University of Leipzig , Leipzig , Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Hensch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001143:Arousal / Q000235:genetics* / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012146:Rest; D012890:Sleep / Q000235:genetics* / Q000502:physiology; D012894:Sleep Stages / Q000502:physiology; D055815:Young Adult
keywords: COMT Val158Met; DRD4 Exon III VNTR; VIGALL; actigraph; arousal; chronotypes; circadian rhythm; rs4680; sleep; vigilance