title: A genome-wide association study of caffeine-related sleep disturbance: confirmation of a role for a common variant in the adenosine receptor.
abstract: OBJECTIVE
  To identify common genetic variants that predispose to caffeine-induced insomnia and to test whether genes whose expression changes in the presence of caffeine are enriched for association with caffeine-induced insomnia.
  
  
  METHODS
  A hypothesis-free, genome-wide association study.
  
  
  METHODS
  Community-based sample of Australian twins from the Australian Twin Registry.
  
  
  METHODS
  After removal of individuals who said that they do not drink coffee, a total of 2,402 individuals from 1,470 families in the Australian Twin Registry provided both phenotype and genotype information.
  
  
  RESULTS
  A dichotomized scale based on whether participants reported ever or never experiencing caffeine-induced insomnia. A factor score based on responses to a number of questions regarding normal sleep habits was included as a covariate in the analysis. More than 2 million common single nucleotide polymorphisms (SNPs) were tested for association with caffeine-induced insomnia. No SNPs reached the genome-wide significance threshold. In the analysis that did not include the insomnia factor score as a covariate, the most significant SNP identified was an intronic SNP in the PRIMA1 gene (P = 1.4 × 10⁻⁶, odds ratio = 0.68 [0.53 - 0.89]). An intergenic SNP near the GBP4 gene on chromosome 1 was the most significant upon inclusion of the insomnia factor score into the model (P = 1.9 × 10⁻⁶, odds ratio = 0.70 [0.62 - 0.78]). A previously identified association with a polymorphism in the ADORA2A gene was replicated.
  
  
  CONCLUSIONS
  Several genes have been identified in the study as potentially influencing caffeine-induced insomnia. They will require replication in another sample. The results may have implications for understanding the biologic mechanisms underlying insomnia.
authors: Queensland Institute of Medical Research, Brisbane, Australia. enda.byrne@qimr.edu.au
authors: Enda M
authors: EM
authors: Byrne
authors: Julie
authors: J
authors: Johnson
authors: Allan F
authors: AF
authors: McRae
authors: Dale R
authors: DR
authors: Nyholt
authors: Sarah E
authors: SE
authors: Medland
authors: Philip R
authors: PR
authors: Gehrman
authors: Andrew C
authors: AC
authors: Heath
authors: Pamela A F
authors: PA
authors: Madden
authors: Grant W
authors: GW
authors: Montgomery
authors: Georgia
authors: G
authors: Chenevix-Trench
authors: Nicholas G
authors: NG
authors: Martin
mesh_terms: D000328:Adult; D002110:Caffeine / Q000009:adverse effects*; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D043705:Receptor, Adenosine A2A / Q000235:genetics* / Q000502:physiology; D012893:Sleep Wake Disorders / Q000139:chemically induced / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C446290:PRIMA1 protein, human; D043705:Receptor, Adenosine A2A; D002110:Caffeine