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Springer Nature [academic journals on], European Journal of Human Genetics, 10(24), p. 1488-1495

DOI: 10.1038/ejhg.2016.31



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Genetic variants in RBFOX3 are associated with sleep latency

Journal article published in 2016 by Najaf Amin, Karla V. Allebrandt, Ashley van der Spek, Bertram Müller-Myhsok, Karin Hek ORCID, Maris Teder-Laving, Caroline Hayward, Tõnu Esko, Josine G. van Mill, J. van Mill, Hamdi Mbarek, Nathaniel F. (Nathaniel F) Watson, Scott A. (Scott) Melville, Fabiola M. (Fabiola) Del Greco, Enda M. (Enda) Byrne and other authors.
This paper is available in a repository.
This paper is available in a repository.

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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 x 10(-08), 6.59 x 10(-08) and 9.17 x 10(-08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values = 1.5 x 10(-02), 7.0 x 10(-03) and 2.5 x 10(-03); combined meta-analysis P-values = 5.5 x 10(-07), 5.4 x 10(-07) and 1.0 x 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 x 10(-316)) and the central nervous system (P-value = 7.5 x 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