GWAS STUDY OF CAFFEINE-RELATED SLEEP DISTURBANCE
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, PhD1,2; Julie Johnson, BSc1,2; Allan F. McRae, PhD1; Dale R. Nyholt, PhD1; Sarah E. Medland, PhD1; Philip R. Gehrman, PhD3; Andrew C. Heath, DPhil4; Pamela A.F. Madden, PhD4; Grant W. Montgomery, PhD1; Georgia Chenevix-Trench, PhD1; Nicholas G. Martin, PhD1
1Queensland Institute of Medical Research, Brisbane, Australia; 2University of Queensland, Brisbane, Australia; 3Behavioral Sleep Medicine Program, Department of Psychiatry and Penn Sleep Center, University of Pennsylvania, Philadelphia; 4Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri
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.
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.
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.
Byrne EM; Johnson J; McRae AF; Nyholt DR; Medland SE; Gehrman PR; Heath AC; Madden PAF; Montgomery GW; Chenevix-Trench G; Martin NG. A genome-wide association study of caffeine-related sleep disturbance: confirmation of a role for a common variant in the adenosine receptor. SLEEP 2012;35(7):967-975.