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Genetic variants in RBFOX3 are associated with sleep latency.


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.

SUBMITTER: Amin N 

PROVIDER: S-EPMC5027680 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Genetic variants in RBFOX3 are associated with sleep latency.

Amin Najaf N   Allebrandt Karla V KV   van der Spek Ashley A   Müller-Myhsok Bertram B   Hek Karin K   Teder-Laving Maris M   Hayward Caroline C   Esko Tõnu T   van Mill Josine G JG   Mbarek Hamdi H   Watson Nathaniel F NF   Melville Scott A SA   Del Greco Fabiola M FM   Byrne Enda M EM   Oole Edwin E   Kolcic Ivana I   Chen Ting-Hsu TH   Evans Daniel S DS   Coresh Josef J   Vogelzangs Nicole N   Karjalainen Juha J   Willemsen Gonneke G   Gharib Sina A SA   Zgaga Lina L   Mihailov Evelin E   Stone Katie L KL   Campbell Harry H   Brouwer Rutger Ww RW   Demirkan Ayse A   Isaacs Aaron A   Dogas Zoran Z   Marciante Kristin D KD   Campbell Susan S   Borovecki Fran F   Luik Annemarie I AI   Li Man M   Hottenga Jouke Jan JJ   Huffman Jennifer E JE   van den Hout Mirjam Cgn MC   Cummings Steven R SR   Aulchenko Yurii S YS   Gehrman Philip R PR   Uitterlinden André G AG   Wichmann Heinz-Erich HE   Müller-Nurasyid Martina M   Fehrmann Rudolf Sn RS   Montgomery Grant W GW   Hofman Albert A   Kao Wen Hong Linda WH   Oostra Ben A BA   Wright Alan F AF   Vink Jacqueline M JM   Wilson James F JF   Pramstaller Peter P PP   Hicks Andrew A AA   Polasek Ozren O   Punjabi Naresh M NM   Redline Susan S   Psaty Bruce M BM   Heath Andrew C AC   Merrow Martha M   Tranah Gregory J GJ   Gottlieb Daniel J DJ   Boomsma Dorret I DI   Martin Nicholas G NG   Rudan Igor I   Tiemeier Henning H   van IJcken Wilfred Fj WF   Penninx Brenda W BW   Metspalu Andres A   Meitinger Thomas T   Franke Lude L   Roenneberg Till T   van Duijn Cornelia M CM  

European journal of human genetics : EJHG 20160504 10


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 fou  ...[more]

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