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
Division of Sleep and Circadian Disorders
Brigham and Women’s Hospital
Boston University
National Heart Lung and Blood Institute’s and Boston University’s Framingham Heart Study
Department of Epidemiology
Erasmus University Rotterdam
Department of Psychiatry
Department of Neurology
University of Washington
Icelandic Heart Association
University of Queensland
Queensland Institute of Medical Research
Harvard University
Stanford University
Azienda Sanitaria Firenze
Department of Twin Research and Genetic Epidemiology
King's College London
California Pacific Medical Center
Department of Psychiatry and Psychotherapy
University of Greifswald
Institute of Behavioural Sciences
University of Helsinki
Folkhalsan
Department of Epidemiology
Johns Hopkins University
Department of Clinical Chemistry
Fimlab Laboratories
Department of Statistics
The University of Auckland
Department of Kinesiology
Université Laval
Institute of Nutrition and Functional Foods
Department of Epidemiology and Health Services
Group Health Cooperative
University of California at Davis
Department of Biological Psychology
Vrije Universiteit Amsterdam
Precision Medicine
Division of Public Health Sciences
Wake Forest University
Southwest Foundation for Biomedical Research
Department of Prosthodontics
LSU Pennington Biomedical Research Center
Department of General Practice and Primary Health Care
Helsinki University Hospital
National Institute for Health and Welfare
Vaasa Hospital District
Dept. of Int. Med. B-Cardiology
Translational Gerontology Branch
National Institutes of Health
Department of Medicine
University of Mississippi
Department of Psychiatry
University of Pennsylvania
Vanderbilt University
Laboratory of Epidemiology
Department of Psychiatry
Washington University St. Louis
Laboratory of Neurogenetics
Program in Molecular and Genetic Epidemiology
National Heart
Department of Clinical Physiology
Tampere University
Department of Health Studies
The University of Chicago
Department of Internal Medicine
Program in Medical and Population Genetics and Genetic Analysis Platform
Broad Institute
Wellcome Trust
Division of Genetics and Cell Biology
San Raffaele Scientific Institute
University of Trieste
National Research Council of Italy
Department of Biomedical Sciences
University of Sassari
Research Centre of Applied and Preventive Cardiovascular Medicine
University of Turku
Department of Pediatrics
University of California at Los Angeles
University of Iceland
Interfaculty Institute for Genetics and Functional Genomics
Institute for Community Medicine
Netherlands Genomics Initiative
Department of Food Science and Nutrition
Department of Population Health Sciences
University of Wisconsin-Madison
Department of Medicine
GeneSTAR Research Program
Department of Child and Adolescent Psychiatry

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

105 Citations (Scopus)

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 {\texttimes} 10 -9). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 {\texttimes} 10 -4). The strongest combined association was at rs1823125 (P=1.5 {\texttimes} 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

Abstract

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