title: Genetic association of objective sleep phenotypes with a functional polymorphism in the neuropeptide S receptor gene.
abstract: BACKGROUND
  The neuropeptide S receptor (NPSR1) and its ligand neuropeptide S (NPS) have received increased attention in the last few years, as both establish a previously unknown system of neuromodulation. Animal research studies have suggested that NPS may be involved in arousal/wakefulness and may also have a crucial role in sleep regulation. The single nucleotide polymorphism (SNP) rs324981 in NPSR1 has begun to shed light on a function of the NPS-system in human sleep regulation. Due to an amino acid exchange, the T-allele leads to an increased sensitivity of the NPSR1. In the only genome-wide association study to date on circadian sleep parameters in humans, an association was found between rs324981 and regular bedtime. However, the sleep parameters in this study were only measured by self-rating. Therefore, our study aimed to replicate these findings using an objective measure of sleep.
  
  
  METHODS
  The study included n = 393 white subjects (62-79 years) who participated in an actigraphic assessment for determining sleep duration, rest duration, sleep onset, rest onset and sleep onset latency. Genotyping of the SNP rs324981 was performed using the TaqMan OpenArray System.
  
  
  RESULTS
  The genotype at rs324981 was not significantly associated with rest onset (bedtime) or sleep onset (p = .146 and p = .199, respectively). However, the SNP showed a significant effect on sleep- and rest duration (p = .007 and p = .003, respectively). Subjects that were homozygous for the minor T-allele had a significantly decreased sleep- and rest duration compared to A-allele carriers.
  
  
  CONCLUSIONS
  The results of this study indicate that the sleep pattern in humans is influenced by the NPS-system. However, the previously reported association between bedtime and rs324981 could not be confirmed. The current finding of decreased sleep duration in T/T allele carriers is in accordance with studies in rodents reporting similar results after NPS application.
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany; Department of Psychiatry and Psychotherapy, Universität Leipzig, Leipzig, Germany.
authors.forename: Janek
authors.initials: J
authors.lastname: Spada
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany; Department of Psychiatry and Psychotherapy, Universität Leipzig, Leipzig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sander
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany; 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: LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany; 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: LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany; Department of Psychiatry and Psychotherapy, Universität Leipzig, Leipzig, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Mergl
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany; Institute for Medical Informatics, Statistics and Epidemiology (IMISE), Universität Leipzig, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Scholz
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany; Department of Psychiatry and Psychotherapy, Universität Leipzig, Leipzig, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hegerl
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany; Department of Psychiatry and Psychotherapy, Universität Leipzig, Leipzig, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Hensch
mesh_terms: D000367:Age Factors; D000368:Aged; D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012890:Sleep / Q000235:genetics*
chemical_list: C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled