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Genetic variants in RBFOX3 are associated with sleep latency.
Wednesday,2016-08-31 10:26 America/Los_Angeles — zdrager
| Title | Genetic variants in RBFOX3 are associated with sleep latency. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Amin, N, Allebrandt, KV, van der Spek, A, Müller-Myhsok, B, Hek, K, Teder-Laving, M, Hayward, C, Esko, T, van Mill, JG, Mbarek, H, Watson, NF, Melville, SA, Del Greco, FM, Byrne, EM, Oole, E, Kolcic, I, Chen, T-H, Evans, DS, Coresh, J, Vogelzangs, N, Karjalainen, J, Willemsen, G, Gharib, SA, Zgaga, L, Mihailov, E, Stone, KL, Campbell, H, Brouwer, RWw, Demirkan, A, Isaacs, A, Dogas, Z, Marciante, KD, Campbell, S, Borovecki, F, Luik, AI, Li, M, Hottenga, JJ, Huffman, JE, van den Hout, MCgn, Cummings, SR, Aulchenko, YS, Gehrman, PR, Uitterlinden, AG, Wichmann, H-E, Müller-Nurasyid, M, Fehrmann, RSn, Montgomery, GW, Hofman, A, Kao, WHL, Oostra, BA, Wright, AF, Vink, JM, Wilson, JF, Pramstaller, PP, Hicks, AA, Polasek, O, Punjabi, NM, Redline, S, Psaty, BM, Heath, AC, Merrow, M, Tranah, GJ, Gottlieb, DJ, Boomsma, DI, Martin, NG, Rudan, I, Tiemeier, H, van IJcken, WFj, Penninx, BW, Metspalu, A, Meitinger, T, Franke, L, Roenneberg, T, van Duijn, CM |
| Journal | Eur J Hum Genet |
| Volume | 24 |
| Issue | 10 |
| Pagination | 1488-95 |
| Date Published | 2016 Oct |
| ISSN | 1476-5438 |
| Abstract | <p>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.</p> |
| DOI | 10.1038/ejhg.2016.31 |
| Alternate Journal | Eur. J. Hum. Genet. |
| PubMed ID | 27142678 |
| PubMed Central ID | PMC5027680 |