Novel loci associated with usual sleep duration

The CHARGE Consortium Genome-Wide Association Study

D. J. Gottlieb, K. Hek, T. H. Chen, N. F. Watson, G. Eiriksdottir, E. M. Byrne, M. Cornelis, S. C. Warby, S. Bandinelli, L. Cherkas, D. S. Evans, H. J. Grabe, J. Lahti, M. Li, T. Lehtimäki, T. Lumley, K. D. Marciante, L. Pérusse, B. M. Psaty, J. Robbins & 66 others G. J. Tranah, J. M. Vink, J. B. Wilk, J. M. Stafford, C. Bellis, R. Biffar, C. Bouchard, B. Cade, G. C. Curhan, J. G. Eriksson, R. Ewert, L. Ferrucci, T. Fülöp, P. R. Gehrman, R. Goodloe, T. B. Harris, A. C. Heath, D. Hernandez, A. Hofman, J. J. Hottenga, D. J. Hunter, M. K. Jensen, A. D. Johnson, M. Kähönen, L. Kao, P. Kraft, E. K. Larkin, D. S. Lauderdale, A. I. Luik, M. Medici, G. W. Montgomery, A. Palotie, S. R. Patel, G. Pistis, E. Porcu, L. Quaye, O. Raitakari, S. Redline, E. B. Rimm, J. I. Rotter, A. V. Smith, T. D. Spector, A. Teumer, A. G. Uitterlinden, M. C. Vohl, E. Widen, G. Willemsen, T. Young, X. Zhang, Y. Liu, J. Blangero, D. I. Boomsma, V. Gudnason, F. Hu, M. Mangino, N. G. Martin, G. T. O'Connor, K. L. Stone, T. Tanaka, J. Viikari, S. A. Gharib, Naresh M Punjabi, K. Räikkönen, H. Völzke, E. Mignot, H. Tiemeier

Research output: Contribution to journalArticle

Abstract

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10 -9). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10 -4). The strongest combined association was at rs1823125 (P=1.5 × 10 -10, minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)1232-1239
Number of pages8
JournalMolecular Psychiatry
Volume20
Issue number10
DOIs
StatePublished - Oct 29 2015

Fingerprint

Genome-Wide Association Study
Sleep
Psychiatry
Alleles
Intergenic DNA
Chromosomes, Human, Pair 2
Metabolome
Metabolic Diseases
Attention Deficit Disorder with Hyperactivity
Gene Frequency
African Americans
Thyroid Gland
Cardiovascular Diseases
Genome
Morbidity
Mortality
Population

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Gottlieb, D. J., Hek, K., Chen, T. H., Watson, N. F., Eiriksdottir, G., Byrne, E. M., ... Tiemeier, H. (2015). Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study. Molecular Psychiatry, 20(10), 1232-1239. https://doi.org/10.1038/mp.2014.133

Novel loci associated with usual sleep duration : The CHARGE Consortium Genome-Wide Association Study. / Gottlieb, D. J.; Hek, K.; Chen, T. H.; Watson, N. F.; Eiriksdottir, G.; Byrne, E. M.; Cornelis, M.; Warby, S. C.; Bandinelli, S.; Cherkas, L.; Evans, D. S.; Grabe, H. J.; Lahti, J.; Li, M.; Lehtimäki, T.; Lumley, T.; Marciante, K. D.; Pérusse, L.; Psaty, B. M.; Robbins, J.; Tranah, G. J.; Vink, J. M.; Wilk, J. B.; Stafford, J. M.; Bellis, C.; Biffar, R.; Bouchard, C.; Cade, B.; Curhan, G. C.; Eriksson, J. G.; Ewert, R.; Ferrucci, L.; Fülöp, T.; Gehrman, P. R.; Goodloe, R.; Harris, T. B.; Heath, A. C.; Hernandez, D.; Hofman, A.; Hottenga, J. J.; Hunter, D. J.; Jensen, M. K.; Johnson, A. D.; Kähönen, M.; Kao, L.; Kraft, P.; Larkin, E. K.; Lauderdale, D. S.; Luik, A. I.; Medici, M.; Montgomery, G. W.; Palotie, A.; Patel, S. R.; Pistis, G.; Porcu, E.; Quaye, L.; Raitakari, O.; Redline, S.; Rimm, E. B.; Rotter, J. I.; Smith, A. V.; Spector, T. D.; Teumer, A.; Uitterlinden, A. G.; Vohl, M. C.; Widen, E.; Willemsen, G.; Young, T.; Zhang, X.; Liu, Y.; Blangero, J.; Boomsma, D. I.; Gudnason, V.; Hu, F.; Mangino, M.; Martin, N. G.; O'Connor, G. T.; Stone, K. L.; Tanaka, T.; Viikari, J.; Gharib, S. A.; Punjabi, Naresh M; Räikkönen, K.; Völzke, H.; Mignot, E.; Tiemeier, H.

In: Molecular Psychiatry, Vol. 20, No. 10, 29.10.2015, p. 1232-1239.

Research output: Contribution to journalArticle

Gottlieb, DJ, Hek, K, Chen, TH, Watson, NF, Eiriksdottir, G, Byrne, EM, Cornelis, M, Warby, SC, Bandinelli, S, Cherkas, L, Evans, DS, Grabe, HJ, Lahti, J, Li, M, Lehtimäki, T, Lumley, T, Marciante, KD, Pérusse, L, Psaty, BM, Robbins, J, Tranah, GJ, Vink, JM, Wilk, JB, Stafford, JM, Bellis, C, Biffar, R, Bouchard, C, Cade, B, Curhan, GC, Eriksson, JG, Ewert, R, Ferrucci, L, Fülöp, T, Gehrman, PR, Goodloe, R, Harris, TB, Heath, AC, Hernandez, D, Hofman, A, Hottenga, JJ, Hunter, DJ, Jensen, MK, Johnson, AD, Kähönen, M, Kao, L, Kraft, P, Larkin, EK, Lauderdale, DS, Luik, AI, Medici, M, Montgomery, GW, Palotie, A, Patel, SR, Pistis, G, Porcu, E, Quaye, L, Raitakari, O, Redline, S, Rimm, EB, Rotter, JI, Smith, AV, Spector, TD, Teumer, A, Uitterlinden, AG, Vohl, MC, Widen, E, Willemsen, G, Young, T, Zhang, X, Liu, Y, Blangero, J, Boomsma, DI, Gudnason, V, Hu, F, Mangino, M, Martin, NG, O'Connor, GT, Stone, KL, Tanaka, T, Viikari, J, Gharib, SA, Punjabi, NM, Räikkönen, K, Völzke, H, Mignot, E & Tiemeier, H 2015, 'Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study', Molecular Psychiatry, vol. 20, no. 10, pp. 1232-1239. https://doi.org/10.1038/mp.2014.133
Gottlieb DJ, Hek K, Chen TH, Watson NF, Eiriksdottir G, Byrne EM et al. Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study. Molecular Psychiatry. 2015 Oct 29;20(10):1232-1239. https://doi.org/10.1038/mp.2014.133
Gottlieb, D. J. ; Hek, K. ; Chen, T. H. ; Watson, N. F. ; Eiriksdottir, G. ; Byrne, E. M. ; Cornelis, M. ; Warby, S. C. ; Bandinelli, S. ; Cherkas, L. ; Evans, D. S. ; Grabe, H. J. ; Lahti, J. ; Li, M. ; Lehtimäki, T. ; Lumley, T. ; Marciante, K. D. ; Pérusse, L. ; Psaty, B. M. ; Robbins, J. ; Tranah, G. J. ; Vink, J. M. ; Wilk, J. B. ; Stafford, J. M. ; Bellis, C. ; Biffar, R. ; Bouchard, C. ; Cade, B. ; Curhan, G. C. ; Eriksson, J. G. ; Ewert, R. ; Ferrucci, L. ; Fülöp, T. ; Gehrman, P. R. ; Goodloe, R. ; Harris, T. B. ; Heath, A. C. ; Hernandez, D. ; Hofman, A. ; Hottenga, J. J. ; Hunter, D. J. ; Jensen, M. K. ; Johnson, A. D. ; Kähönen, M. ; Kao, L. ; Kraft, P. ; Larkin, E. K. ; Lauderdale, D. S. ; Luik, A. I. ; Medici, M. ; Montgomery, G. W. ; Palotie, A. ; Patel, S. R. ; Pistis, G. ; Porcu, E. ; Quaye, L. ; Raitakari, O. ; Redline, S. ; Rimm, E. B. ; Rotter, J. I. ; Smith, A. V. ; Spector, T. D. ; Teumer, A. ; Uitterlinden, A. G. ; Vohl, M. C. ; Widen, E. ; Willemsen, G. ; Young, T. ; Zhang, X. ; Liu, Y. ; Blangero, J. ; Boomsma, D. I. ; Gudnason, V. ; Hu, F. ; Mangino, M. ; Martin, N. G. ; O'Connor, G. T. ; Stone, K. L. ; Tanaka, T. ; Viikari, J. ; Gharib, S. A. ; Punjabi, Naresh M ; Räikkönen, K. ; Völzke, H. ; Mignot, E. ; Tiemeier, H. / Novel loci associated with usual sleep duration : The CHARGE Consortium Genome-Wide Association Study. In: Molecular Psychiatry. 2015 ; Vol. 20, No. 10. pp. 1232-1239.
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TY - JOUR

T1 - Novel loci associated with usual sleep duration

T2 - The CHARGE Consortium Genome-Wide Association Study

AU - Gottlieb, D. J.

AU - Hek, K.

AU - Chen, T. H.

AU - Watson, N. F.

AU - Eiriksdottir, G.

AU - Byrne, E. M.

AU - Cornelis, M.

AU - Warby, S. C.

AU - Bandinelli, S.

AU - Cherkas, L.

AU - Evans, D. S.

AU - Grabe, H. J.

AU - Lahti, J.

AU - Li, M.

AU - Lehtimäki, T.

AU - Lumley, T.

AU - Marciante, K. D.

AU - Pérusse, L.

AU - Psaty, B. M.

AU - Robbins, J.

AU - Tranah, G. J.

AU - Vink, J. M.

AU - Wilk, J. B.

AU - Stafford, J. M.

AU - Bellis, C.

AU - Biffar, R.

AU - Bouchard, C.

AU - Cade, B.

AU - Curhan, G. C.

AU - Eriksson, J. G.

AU - Ewert, R.

AU - Ferrucci, L.

AU - Fülöp, T.

AU - Gehrman, P. R.

AU - Goodloe, R.

AU - Harris, T. B.

AU - Heath, A. C.

AU - Hernandez, D.

AU - Hofman, A.

AU - Hottenga, J. J.

AU - Hunter, D. J.

AU - Jensen, M. K.

AU - Johnson, A. D.

AU - Kähönen, M.

AU - Kao, L.

AU - Kraft, P.

AU - Larkin, E. K.

AU - Lauderdale, D. S.

AU - Luik, A. I.

AU - Medici, M.

AU - Montgomery, G. W.

AU - Palotie, A.

AU - Patel, S. R.

AU - Pistis, G.

AU - Porcu, E.

AU - Quaye, L.

AU - Raitakari, O.

AU - Redline, S.

AU - Rimm, E. B.

AU - Rotter, J. I.

AU - Smith, A. V.

AU - Spector, T. D.

AU - Teumer, A.

AU - Uitterlinden, A. G.

AU - Vohl, M. C.

AU - Widen, E.

AU - Willemsen, G.

AU - Young, T.

AU - Zhang, X.

AU - Liu, Y.

AU - Blangero, J.

AU - Boomsma, D. I.

AU - Gudnason, V.

AU - Hu, F.

AU - Mangino, M.

AU - Martin, N. G.

AU - O'Connor, G. T.

AU - Stone, K. L.

AU - Tanaka, T.

AU - Viikari, J.

AU - Gharib, S. A.

AU - Punjabi, Naresh M

AU - Räikkönen, K.

AU - Völzke, H.

AU - Mignot, E.

AU - Tiemeier, H.

PY - 2015/10/29

Y1 - 2015/10/29

N2 - Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10 -9). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10 -4). The strongest combined association was at rs1823125 (P=1.5 × 10 -10, minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

AB - Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10 -9). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10 -4). The strongest combined association was at rs1823125 (P=1.5 × 10 -10, minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

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