A genome-wide association study of caffeine-related sleep disturbance: Confirmation of a role for a common variant in the adenosine receptor

Enda M. Byrne, Julie Johnson, Allan F. McRae, Dale R. Nyholt, Sarah E. Medland, Philip R. Gehrman, Andrew C. Heath, Pamela A.F. Madden, Grant W. Montgomery, Georgia Chenevix-Trench, Nicholas G. Martin

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Objectives: 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. Design: A hypothesis-free, genome-wide association study. Setting: Community-based sample of Australian twins from the Australian Twin Registry. Participants: 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. Measurements and 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.

Original languageEnglish
Pages (from-to)967-975
Number of pages9
JournalSleep
Volume35
Issue number7
DOIs
StatePublished - Jul 1 2012

Keywords

  • Caffeine
  • Genetics
  • Insomnia

Fingerprint

Dive into the research topics of 'A genome-wide association study of caffeine-related sleep disturbance: Confirmation of a role for a common variant in the adenosine receptor'. Together they form a unique fingerprint.

Cite this