Genetic variants in <i>RBFOX3</i> are associated with sleep latency


Amin, Najaf, Allebrandt, Karla V, van der Spek, Ashley, Mueller-Myhsok, Bertram ORCID: 0000-0002-0719-101X, Hek, Karin, Teder-Laving, Maris, Hayward, Caroline, Esko, Tonu, van Mill, Josine G, Mbarek, Hamdi et al (show 64 more authors) (2016) Genetic variants in <i>RBFOX3</i> are associated with sleep latency. EUROPEAN JOURNAL OF HUMAN GENETICS, 24 (10). pp. 1488-1495.

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: Brain, Humans, Nerve Tissue Proteins, Antigens, Nuclear, Sleep, Synaptic Transmission, Polymorphism, Single Nucleotide
Depositing User: Symplectic Admin
Date Deposited: 16 Sep 2016 08:57
Last Modified: 18 Oct 2023 09:55
DOI: 10.1038/ejhg.2016.31
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3003327
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