2016-05-04
Genetic variants in RBFOX3 are associated with sleep latency
Publication
Publication
Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta-analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P-values=5.77 × 10-08, 6.59 × 10- 08 and 9.17 × 10- 08). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 × 10- 02, 7.0 × 10- 03 and 2.5 × 10- 03; combined meta-analysis P-values=5.5 × 10-07, 5.4 × 10-07 and 1.0 × 10-07). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 × 10-316) and the central nervous system (P-value=7.5 × 10- 321). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values<2.9 × 10-11) that are crucial in triggering the onset of sleep. To conclude, in this first large-scale GWAS of sleep latency we report a novel association of variants in RBFOX3 gene. Further, a functional prediction of RBFOX3 supports the involvement of RBFOX3 with sleep latency.European Journal of Human Genetics advance online publication, 4 May 2016; doi:10.1038/ejhg.2016.31.
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| doi.org/10.1038/ejhg.2016.31, hdl.handle.net/1765/81173 | |
| European Journal of Human Genetics | |
| Organisation | Department of Epidemiology |
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Amin, N., Allebrandt, K. V., van der Spek, A., Müller-Myhsok, B., Hek, K., Teder-Laving, M., … van Duijn, C. (2016). Genetic variants in RBFOX3 are associated with sleep latency. European Journal of Human Genetics. doi:10.1038/ejhg.2016.31 |
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