| Literature DB >> 27142678 |
Najaf Amin1, Karla V Allebrandt2, Ashley van der Spek1, Bertram Müller-Myhsok3, Karin Hek4,5, Maris Teder-Laving6, Caroline Hayward7, Tõnu Esko6, Josine G van Mill8, Hamdi Mbarek9, Nathaniel F Watson10,11, Scott A Melville12, Fabiola M Del Greco13, Enda M Byrne14,15, Edwin Oole16, Ivana Kolcic17, Ting-Hsu Chen18, Daniel S Evans19, Josef Coresh20, Nicole Vogelzangs8, Juha Karjalainen21, Gonneke Willemsen9, Sina A Gharib11,22, Lina Zgaga7, Evelin Mihailov6, Katie L Stone19, Harry Campbell23, Rutger Ww Brouwer16, Ayse Demirkan1, Aaron Isaacs1, Zoran Dogas24, Kristin D Marciante25, Susan Campbell7, Fran Borovecki26, Annemarie I Luik4, Man Li27, Jouke Jan Hottenga9, Jennifer E Huffman7, Mirjam Cgn van den Hout16, Steven R Cummings19, Yurii S Aulchenko1, Philip R Gehrman28, André G Uitterlinden4,29,30, Heinz-Erich Wichmann31,32,33, Martina Müller-Nurasyid31,34,35,36, Rudolf Sn Fehrmann21, Grant W Montgomery15, Albert Hofman4,37, Wen Hong Linda Kao27, Ben A Oostra1, Alan F Wright7, Jacqueline M Vink9, James F Wilson7,23, Peter P Pramstaller13,38,39, Andrew A Hicks13, Ozren Polasek17,40, Naresh M Punjabi41, Susan Redline42, Bruce M Psaty43,44, Andrew C Heath45, Martha Merrow2, Gregory J Tranah19, Daniel J Gottlieb42,46, Dorret I Boomsma9, Nicholas G Martin15, Igor Rudan23, Henning Tiemeier4,5,47, Wilfred Fj van IJcken16, Brenda W Penninx8, Andres Metspalu6, Thomas Meitinger48,49, Lude Franke21, Till Roenneberg2, Cornelia M van Duijn1,30,50.
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.Entities:
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Year: 2016 PMID： 27142678 PMCID： PMC5027680 DOI： 10.1038/ejhg.2016.31
Source DB: PubMed Journal: Eur J Hum Genet ISSN： 1018-4813 Impact factor: 4.246