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. RobbinsG. 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

    Research output: Contribution to journalArticlepeer-review

    60 Scopus citations

    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

    ASJC Scopus subject areas

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

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