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

Byrne, Enda M., Johnson, Julie, McRae, Allan F., Nyholt, Dale R., Medland, Sarah E., Gehrman, Philip R., Heath, Andrew C., Madden, Pamela A.F., Montgomery, Grant W., Chenevix-Trench, Georgia, & Martin, Nicholas G. (2012) A genome-wide association study of caffeine-related sleep disturbance: Confirmation of a role for a common variant in the adenosine receptor. Sleep, 35(7), pp. 967-975.

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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.


A hypothesis-free, genome-wide association study.


Community-based sample of Australian twins from the Australian Twin Registry.


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.


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 x 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 x 10(-)(6), odds ratio = 0.70 [0.62 - 0.78]). A previously identified association with a polymorphism in the ADORA2A gene was replicated.


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.

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ID Code: 91849
Item Type: Journal Article
Refereed: Yes
Additional Information: Australian National Health and Medical Research Council
(241944, 339462, 389927, 389875, 389891, 389892, 389938,
442915, 442981, 496739, 552485, 552498, 613608), the Australian
Research Council (A7960034, A79906588, A79801419,
DP0770096, DP0212016, DP0343921
Keywords: Adult, Caffeine/*adverse effects, Female, Gene Expression Profiling, *Genome-Wide Association Study, Genotype, Humans, Male, Membrane Proteins/genetics/physiology, Nerve Tissue Proteins/genetics/physiology, Polymorphism, Single Nucleotide/*genetics, Receptor, Adenosine A2A/*genetics/physiology, Sleep Disorders/chemically induced/*genetics
DOI: 10.5665/sleep.1962
ISSN: 1550-9109
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 14 Jan 2016 00:35
Last Modified: 03 Apr 2017 04:24

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