Dataset Information

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]

PMID: 27142678

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Genetic variants in RBFOX3 are associated with sleep latency.

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Genetic variants in RBFOX3 are associated with sleep latency.

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