SLEEP - A Genome-Wide Association Study of Caffeine-Related Sleep Disturbance: Confirmation of a Role for a Common Variant in the Adenosine Receptor

VOLUME 35, ISSUE 07

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

http://dx.doi.org/10.5665/sleep.1962

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

Table of Contents

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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.

Citation:

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.