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; 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; N. M. Punjabi; K. Räikkönen; H. Völzke; E. Mignot; H. Tiemeier

doi:10.1038/mp.2014.133

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

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, N. M. Punjabi, K. Räikkönen, H. Völzke, E. Mignot, H. Tiemeier

^*Corresponding author for this work

Department of Veterans Affairs
Brigham and Women’s Hospital
Boston University
National Heart Lung and Blood Institute’s and Boston University’s Framingham Heart Study
Erasmus University Rotterdam
University of Washington
Icelandic Heart Association
University of Queensland
Queensland Institute of Medical Research
Harvard University
Stanford University
Azienda Sanitaria Firenze
King's College London
California Pacific Medical Center
University of Greifswald
University of Helsinki
Folkhalsan
Johns Hopkins University
Fimlab Laboratories
The University of Auckland
Université Laval
Group Health Cooperative
University of California at Davis
Vrije Universiteit Amsterdam
Precision Medicine
Wake Forest University
Southwest Foundation for Biomedical Research
LSU Pennington Biomedical Research Center
Helsinki University Hospital
National Institute for Health and Welfare
Vaasa Hospital District
National Institutes of Health
University of Mississippi
University of Pennsylvania
Vanderbilt University
Washington University St. Louis
Tampere University
The University of Chicago
Broad Institute
Wellcome Trust
San Raffaele Scientific Institute
University of Trieste
National Research Council of Italy
University of Sassari
University of Turku
University of California at Los Angeles
University of Iceland
Netherlands Genomics Initiative
University of Wisconsin-Madison

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	1232-1239
Number of pages	8
Journal	Molecular Psychiatry
Volume	20
Issue number	10
DOIs	https://doi.org/10.1038/mp.2014.133
Publication status	Published - 29 Oct 2015
Externally published	Yes

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10.1038/mp.2014.133

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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., ... 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

@article{5ce9a20a3d4d40d6917d7f57cce2baad,

title = "Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study",

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.",

author = "Gottlieb, \{D. J.\} and K. Hek and Chen, \{T. H.\} and Watson, \{N. F.\} and G. Eiriksdottir and Byrne, \{E. M.\} and M. Cornelis and Warby, \{S. C.\} and S. Bandinelli and L. Cherkas and Evans, \{D. S.\} and Grabe, \{H. J.\} and J. Lahti and M. Li and T. Lehtim{\"a}ki and T. Lumley and Marciante, \{K. D.\} and L. P{\'e}russe and Psaty, \{B. M.\} and J. Robbins and Tranah, \{G. J.\} and Vink, \{J. M.\} and Wilk, \{J. B.\} and Stafford, \{J. M.\} and C. Bellis and R. Biffar and C. Bouchard and B. Cade and Curhan, \{G. C.\} and Eriksson, \{J. G.\} and R. Ewert and L. Ferrucci and T. F{\"u}l{\"o}p and Gehrman, \{P. R.\} and R. Goodloe and Harris, \{T. B.\} and Heath, \{A. C.\} and D. Hernandez and A. Hofman and Hottenga, \{J. J.\} and Hunter, \{D. J.\} and Jensen, \{M. K.\} and Johnson, \{A. D.\} and M. K{\"a}h{\"o}nen and L. Kao and P. Kraft and Larkin, \{E. K.\} and Lauderdale, \{D. S.\} and Luik, \{A. I.\} and M. Medici and Montgomery, \{G. W.\} and A. Palotie and Patel, \{S. R.\} and G. Pistis and E. Porcu and L. Quaye and O. Raitakari and S. Redline and Rimm, \{E. B.\} and Rotter, \{J. I.\} and Smith, \{A. V.\} and Spector, \{T. D.\} and A. Teumer and Uitterlinden, \{A. G.\} and Vohl, \{M. C.\} and E. Widen and G. Willemsen and T. Young and X. Zhang and Y. Liu and J. Blangero and Boomsma, \{D. I.\} and V. Gudnason and F. Hu and M. Mangino and Martin, \{N. G.\} and O'Connor, \{G. T.\} and Stone, \{K. L.\} and T. Tanaka and J. Viikari and Gharib, \{S. A.\} and Punjabi, \{N. M.\} and K. R{\"a}ikk{\"o}nen and H. V{\"o}lzke and E. Mignot and H. Tiemeier",

year = "2015",

month = oct,

day = "29",

doi = "10.1038/mp.2014.133",

language = "English",

volume = "20",

pages = "1232--1239",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Springer Nature",

number = "10",

}

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

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, N. 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.

UR - https://www.scopus.com/pages/publications/84942551376

U2 - 10.1038/mp.2014.133

DO - 10.1038/mp.2014.133

M3 - Article

C2 - 25469926

AN - SCOPUS:84942551376

SN - 1359-4184

VL - 20

SP - 1232

EP - 1239

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 10

ER -

Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study

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