Genetic variants in RBFOX3 are associated with sleep latency View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-10

AUTHORS

Najaf Amin, Karla V Allebrandt, Ashley van der Spek, Bertram Müller-Myhsok, Karin Hek, Maris Teder-Laving, Caroline Hayward, Tõnu Esko, Josine G van Mill, Hamdi Mbarek, Nathaniel F Watson, Scott A Melville, Fabiola M Del Greco, Enda M Byrne, Edwin Oole, Ivana Kolcic, Ting-Hsu Chen, Daniel S Evans, Josef Coresh, Nicole Vogelzangs, Juha Karjalainen, Gonneke Willemsen, Sina A Gharib, Lina Zgaga, Evelin Mihailov, Katie L Stone, Harry Campbell, Rutger Ww Brouwer, Ayse Demirkan, Aaron Isaacs, Zoran Dogas, Kristin D Marciante, Susan Campbell, Fran Borovecki, Annemarie I Luik, Man Li, Jouke Jan Hottenga, Jennifer E Huffman, Mirjam Cgn van den Hout, Steven R Cummings, Yurii S Aulchenko, Philip R Gehrman, André G Uitterlinden, Heinz-Erich Wichmann, Martina Müller-Nurasyid, Rudolf Sn Fehrmann, Grant W Montgomery, Albert Hofman, Wen Hong Linda Kao, Ben A Oostra, Alan F Wright, Jacqueline M Vink, James F Wilson, Peter P Pramstaller, Andrew A Hicks, Ozren Polasek, Naresh M Punjabi, Susan Redline, Bruce M Psaty, Andrew C Heath, Martha Merrow, Gregory J Tranah, Daniel J Gottlieb, Dorret I Boomsma, Nicholas G Martin, Igor Rudan, Henning Tiemeier, Wilfred Fj van IJcken, Brenda W Penninx, Andres Metspalu, Thomas Meitinger, Lude Franke, Till Roenneberg, Cornelia M van Duijn

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. More... »

PAGES

1488-1495

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ejhg.2016.31

DOI

http://dx.doi.org/10.1038/ejhg.2016.31

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022956881

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27142678


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71 schema:description 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.
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