Genetic variants in RBFOX3 are associated with sleep latency

被引:25
作者
Amin, Najaf [1 ]
Allebrandt, Karla V. [2 ]
van der Spek, Ashley [1 ]
Mueller-Myhsok, Bertram [3 ]
Hek, Karin [4 ,5 ]
Teder-Laving, Maris [6 ,7 ]
Hayward, Caroline [8 ]
Esko, Tonu [6 ,7 ]
van Mill, Josine G. [9 ]
Mbarek, Hamdi [10 ]
Watson, Nathaniel F. [11 ,12 ]
Melville, Scott A. [13 ]
Del Greco, Fabiola M. [14 ,15 ]
Byrne, Enda M. [16 ,17 ]
Oole, Edwin [18 ]
Kolcic, Ivana [19 ]
Chen, Ting-hsu [20 ]
Evans, Daniel S. [21 ]
Coresh, Josef [22 ,23 ,24 ]
Vogelzangs, Nicole [9 ]
Karjalainen, Juha [25 ]
Willemsen, Gonneke [10 ]
Gharib, Sina A. [12 ,13 ,26 ]
Zgaga, Lina
Mihailov, Evelin [6 ,7 ]
Stone, Katie L. [21 ]
Campbell, Harry [27 ]
Brouwer, Rutger Ww [18 ]
Demirkan, Ayse [1 ]
Isaacs, Aaron [1 ]
Dogas, Zoran [28 ,29 ]
Marciante, Kristin D. [30 ]
Campbell, Susan [8 ]
Borovecki, Fran [31 ,32 ]
Luik, Annemarie I. [4 ]
Li, Man [33 ]
Hottenga, Jouke Jan [10 ]
Huffman, Jennifer E. [8 ]
van den Hout, Mirjam C. G. N. [18 ]
Cummings, Steven R. [21 ]
Aulchenko, Yuru S. [1 ]
Gehrman, Philip R. [34 ]
Uitterlinden, Andre G. [35 ,36 ]
Wichmann, Heinz-Erich [37 ,38 ,39 ,40 ]
Muller-Nurasyid, Martina [37 ,41 ,42 ,43 ]
Fehrmann, Rudolf S. N. [25 ]
Montgomery, Grant W. [17 ]
Hofman, Albert [44 ]
Kao, Wen Hong Linda [33 ]
Oostra, Ben A. [1 ]
机构
[1] Erasmus Univ, Med Ctr, Dept Epidemiol, Unit Genet Epidemiol, Wytemaweg 80, Rotterdam, Netherlands
[2] Univ Munich, Inst Med Psychol, Munich, Germany
[3] Max Planck Inst Psychiat, Munich, Germany
[4] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands
[5] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands
[6] Univ Tartu, Estonian Genome Ctr, Tartu, Estonia
[7] Estonian Bioctr, Tartu, Estonia
[8] Univ Edinburgh, IGMM, Human Genet Unit, MRC, Edinburgh, Midlothian, Scotland
[9] Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Psychiat, Amsterdam, Netherlands
[10] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands
[11] Univ Washington, Dept Neurol, Seattle, WA 98195 USA
[12] Univ Washington, Med Sleep Ctr, Seattle, WA 98195 USA
[13] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA
[14] European Acad Bolzano, Ctr Biomed, Bolzano, Italy
[15] Univ Lubeck, Lubeck, Germany
[16] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia
[17] Queensland Inst Med Res, Brisbane, Qld, Australia
[18] Erasmus MC, Ctr Biom, Rotterdam, Netherlands
[19] Univ Split, Sch Med, Split, Croatia
[20] Boston Univ, VA Boston Healthcare Syst, Boston, MA 02215 USA
[21] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA
[22] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA
[23] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA
[24] Johns Hopkins Univ, Dept Med, Baltimore, MD USA
[25] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands
[26] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA USA
[27] Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland
[28] Univ Split, Sch Med, Dept Neurosci, Split, Croatia
[29] Univ Split, Sch Med, Sleep Med Ctr, Split, Croatia
[30] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA
[31] Univ Zagreb, Fac Med, Ctr Funct Genom, Zagreb, Croatia
[32] Univ Zagreb, Fac Med, Dept Neurol, Zagreb, Croatia
[33] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA
[34] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA
[35] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands
[36] Netherlands Consortium Hlth Ageing & Natl Genom I, Leiden, Netherlands
[37] German Res Ctr Environm Hlth, Helmholtz Zentrum Munich, 31Institute Epidemiol, Neuherberg, Germany
[38] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany
[39] Klinikum Grosshadern, Munich, Germany
[40] Tech Univ Munich, Inst Med Stat & Epidemiol, Munich, Germany
[41] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany
[42] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany
[43] Partner Site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany
[44] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
[45] Gen Cent Hosp, Dept Neurol, Bolzano, Italy
[46] Univ Lubeck, Dept Neurol, Lubeck, Germany
[47] Univ Split, Sch Med, Ctr Global Hlth, Split, Croatia
[48] Johns Hopkins Univ, Dept Pulm Med & Epidemiol, Baltimore, MD USA
[49] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA
[50] Harvard Med Sch, Beth Deaconess Med Ctr, Boston, MA USA
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
GENOME-WIDE ASSOCIATION; RECORDED SLEEP; CANDIDATE-GENE; SELF-REPORT; EXPRESSION; FAMILY; DETERMINANTS; BRAIN; SEX;
D O I
10.1038/ejhg.2016.31
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 x 10(-08), 6.59 x 10(-08) and 9.17 x 10(-08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values = 1.5 x 10(-02), 7.0 x 10(-03) and 2.5 x 10(-03); combined meta-analysis P-values = 5.5 x 10(-07), 5.4 x 10(-07) and 1.0 x 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 x 10(-316)) and the central nervous system (P-value = 7.5 x 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<2.9x10(-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.
引用
收藏
页码:1488 / 1495
页数:8
相关论文
共 60 条
[1]   High-glycemic-index carbohyorate meals shorten sleep onset [J].
Afaghi, Ahmad ;
O'Connor, Helen ;
Chow, Chin Moi .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 2007, 85 (02) :426-430
[2]   Multipoint quantitative-trait linkage analysis in general pedigrees [J].
Almasy, L ;
Blangero, J .
AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 62 (05) :1198-1211
[3]   Singular value decomposition for genome-wide expression data processing and modeling [J].
Alter, O ;
Brown, PO ;
Botstein, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (18) :10101-10106
[4]   A Genomic Background Based Method for Association Analysis in Related Individuals [J].
Amin, Najaf ;
van Duijn, Cornelia M. ;
Aulchenko, Yurii S. .
PLOS ONE, 2007, 2 (12)
[5]   GenABEL: an R library for genome-wide association analysis [J].
Aulchenko, Yurii S. ;
Ripke, Stephan ;
Isaacs, Aaron ;
Van Duijn, Cornelia M. .
BIOINFORMATICS, 2007, 23 (10) :1294-1296
[6]   ProbABEL package for genome-wide association analysis of imputed data [J].
Aulchenko, Yurii S. ;
Struchalin, Maksim V. ;
van Duijn, Cornelia M. .
BMC BIOINFORMATICS, 2010, 11
[7]  
BAEKELAND F, 1971, ARCH GEN PSYCHIAT, V24, P548
[8]   Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p:: Evidence of association at GRIN2A and ABAT [J].
Barnby, G ;
Abbott, A ;
Sykes, N ;
Morris, A ;
Weeks, DE ;
Mott, R ;
Lamb, J ;
Bailey, AJ ;
Monaco, AP .
AMERICAN JOURNAL OF HUMAN GENETICS, 2005, 76 (06) :950-966
[9]   The de novo chromosome 16 translocations of two patients with abnormal phenotypes (mental retardation and epilepsy) disrupt the A2BP1 gene [J].
Bhalla, K ;
Phillips, HA ;
Crawford, J ;
McKenzie, OLD ;
Mulley, JC ;
Eyre, H ;
Gardner, AE ;
Kremmidiotis, G ;
Callen, DF .
JOURNAL OF HUMAN GENETICS, 2004, 49 (06) :308-311
[10]   Sleep problems of elementary school children - A community survey [J].
Blader, JC ;
Koplewicz, HS ;
Abikoff, H ;
Foley, C .
ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE, 1997, 151 (05) :473-480