Habitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants

Hassan S. Dashti, Jack L. Follis, Caren E. Smith, Toshiko Tanaka, Brian E. Cade, Daniel J. Gottlieb, Adela Hruby, Paul F. Jacques, Stefania Lamon-Fava, Kris Richardson, Richa Saxena, Frank A J L Scheer, Traci M. Bartz, Mia Maria Perälä, Anna Jonsson, Alexis C. Frazier-Wood, Ioanna Panagiota Kalafati, Vera Mikkilä, Timo Partonen, Rozenn N. LemaitreJari Lahti, Dena G. Hernandez, Ulla Toft, W. Craig Johnson, Stavroula Kanoni, Olli T. Raitakari, Markus Perola, Bruce M. Psaty, Luigi Ferrucci, Niels Grarup, Heather M. Highland, Loukianos Rallidis, Mika Kähönen, Aki S. Havulinna, David S. Siscovick, Katri Räikkönen, Torben Jorgensen, Jerome I. Rotter, Panos Deloukas, Jorma S A Viikari, Dariush Mozaffarian, Allan Linneberg, Ilkka Seppälä, Torben Hansen, Veikko Salomaa, Sina A. Gharib, Johan G. Eriksson, Stefania Bandinelli, Oluf Pedersen, Stephen S. Rich, George Dedoussis, Terho Lehtimäki, José M. Ordovás

Research output: Contribution to journalArticlepeer-review


Background: Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake. Objectives: We examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations. Design: We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Results: We observed a significant association between sleep duration and lower BMI (β ± SE = 0.16 ± 0.04, P <0.0001) in the overall sample; however, associations between sleep duration and relative macronutrient intake were evident in age- and sex-stratified analyses only. We observed a significant association between sleep duration and lower saturated fatty acid intake in younger (aged 20-64 y) adults (men: 0.11 ± 0.06%, P = 0.03; women: 0.10 ± 0.05%, P = 0.04) and with lower carbohydrate (-0.31 ± 0.12%, P <0.01), higher total fat (0.18 ± 0.09%, P = 0.05), and higher PUFA (0.05 ± 0.02%, P = 0.02) intakes in older (aged 65-80 y) women. In addition, the following 2 nominally significant interactions were observed: between sleep duration and rs12649507 on PUFA intake and between sleep duration and rs6858749 on protein intake. Conclusions: Our results indicate that longer habitual sleep duration is associated with lower BMI and age- and sex-specific favorable dietary behaviors. Differences in the relative intake of specific macronutrients associated with short sleep duration could, at least in part, explain previously reported associations between short sleep duration and chronic metabolic abnormalities. In addition, the influence of obesity-associated CLOCK variants on the association between sleep duration and macronutrient intake suggests that longer habitual sleep duration could ameliorate the genetic predisposition to obesity via a favorable dietary profile. Trials related to this study were registered at clinicaltrials.gov as NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT01331512 [Invecchiare in Chianti (Aging in the Chianti Area) study], NCT00289237 (Inter99), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).

Original languageEnglish (US)
Pages (from-to)135-143
Number of pages9
JournalAmerican Journal of Clinical Nutrition
Issue number1
StatePublished - Jan 1 2015
Externally publishedYes


  • Circadian rhythm
  • Dietary intake
  • Gene-environment interaction
  • Sleep duration

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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