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

作者：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

来源：SLEEP, 2012, 35(7): 967-975.

DOI：10.5665/sleep.1962

• Caffeine
• insomnia
• genetics

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 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.
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.

• 出版日期2012-7-1
• 单位河北医科大学