Genetic variants in RBFOX3 are associated with sleep latency

Amin, Najaf, Allebrandt, Karla V., van der Spek, Ashley, Müller-Myhsok, Bertram, Hek, Karin, Teder-Laving, Maris, Hayward, Caroline, Esko, Tõnu, van Mill, Josine G., Mbarek, Hamdi, Watson, Nathaniel F., Melville, Scott A., Del Greco, Fabiola M., Byrne, Enda M., Oole, Edwin, Kolcic, Ivana, Chen, Ting-hsu, Evans, Daniel S., Coresh, Josef, Vogelzangs, Nicole, Karjalainen, Juha, Willemsen, Gonneke, Gharib, Sina A., Zgaga, Lina, Mihailov, Evelin, Stone, Katie L., Campbell, Harry, Brouwer, Rutger W. W., Demirkan, Ayse, Isaacs, Aaron, Dogas, Zoran, Marciante, Kristin D., Campbell, Susan, Borovecki, Fran, Luik, Annemarie I., Li, Man, Hottenga, Jouke Jan, Huffman, Jennifer E., van den Hout, Mirjam C. G. N., Cummings, Steven R., Aulchenko, Yurii S., Gehrman, Philip R., Uitterlinden, André G., Wichmann, Heinz-Erich, Müller-Nurasyid, Martina, Fehrmann, Rudolf S. N., Montgomery, Grant W., Hofman, Albert, Kao, Wen Hong Linda, Oostra, Ben A., Wright, Alan F., Vink, Jacqueline M., Wilson, James F., Pramstaller, Peter P., Hicks, Andrew A., Polasek, Ozren, Punjabi, Naresh M., Redline, Susan, Psaty, Bruce M., Heath, Andrew C., Merrow, Martha, Tranah, Gregory J., Gottlieb, Daniel J., Boomsma, Dorret I., Martin, Nicholas G., Rudan, Igor, Tiemeier, Henning, van IJcken, Wilfred F. J., Penninx, Brenda W., Metspalu, Andres, Meitinger, Thomas, Franke, Lude, Roenneberg, Till and van Duijn, Cornelia M. (2016) Genetic variants in RBFOX3 are associated with sleep latency. European Journal of Human Genetics, 24 10: 1488-1495. doi:10.1038/ejhg.2016.31


Author Amin, Najaf
Allebrandt, Karla V.
van der Spek, Ashley
Müller-Myhsok, Bertram
Hek, Karin
Teder-Laving, Maris
Hayward, Caroline
Esko, Tõnu
van Mill, Josine G.
Mbarek, Hamdi
Watson, Nathaniel F.
Melville, Scott A.
Del Greco, Fabiola M.
Byrne, Enda M.
Oole, Edwin
Kolcic, Ivana
Chen, Ting-hsu
Evans, Daniel S.
Coresh, Josef
Vogelzangs, Nicole
Karjalainen, Juha
Willemsen, Gonneke
Gharib, Sina A.
Zgaga, Lina
Mihailov, Evelin
Stone, Katie L.
Campbell, Harry
Brouwer, Rutger W. W.
Demirkan, Ayse
Isaacs, Aaron
Dogas, Zoran
Marciante, Kristin D.
Campbell, Susan
Borovecki, Fran
Luik, Annemarie I.
Li, Man
Hottenga, Jouke Jan
Huffman, Jennifer E.
van den Hout, Mirjam C. G. N.
Cummings, Steven R.
Aulchenko, Yurii S.
Gehrman, Philip R.
Uitterlinden, André G.
Wichmann, Heinz-Erich
Müller-Nurasyid, Martina
Fehrmann, Rudolf S. N.
Montgomery, Grant W.
Hofman, Albert
Kao, Wen Hong Linda
Oostra, Ben A.
Wright, Alan F.
Vink, Jacqueline M.
Wilson, James F.
Pramstaller, Peter P.
Hicks, Andrew A.
Polasek, Ozren
Punjabi, Naresh M.
Redline, Susan
Psaty, Bruce M.
Heath, Andrew C.
Merrow, Martha
Tranah, Gregory J.
Gottlieb, Daniel J.
Boomsma, Dorret I.
Martin, Nicholas G.
Rudan, Igor
Tiemeier, Henning
van IJcken, Wilfred F. J.
Penninx, Brenda W.
Metspalu, Andres
Meitinger, Thomas
Franke, Lude
Roenneberg, Till
van Duijn, Cornelia M.
Title Genetic variants in RBFOX3 are associated with sleep latency
Formatted title
Genetic variants in RBFOX3 are associated with sleep latency
Journal name European Journal of Human Genetics   Check publisher's open access policy
ISSN 1018-4813
1476-5438
Publication date 2016-10-01
Sub-type Article (original research)
DOI 10.1038/ejhg.2016.31
Open Access Status Not yet assessed
Volume 24
Issue 10
Start page 1488
End page 1495
Total pages 8
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
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.
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID K-1206
MC_PC_U127561128
R01 AG030474
R01 HL105756
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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Created: Tue, 27 Sep 2016, 20:25:04 EST by Kirstie Asmussen on behalf of School of Music