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

Author
item DASHTI, HASSAN - Tufts University
item FOLLIS, JACK - University Of St Thomas
item SMITH, CAREN - Tufts University
item TANAKA, TOSHIKO - Translational Genomics Research Institute
item CADE, BRIAN - Brigham & Women'S Hospital
item GOTTLIEB, DANIEL - Brigham & Women'S Hospital
item HRUBY, ADELA - Harvard Institute
item JACQUES, PAUL - Tufts University
item LAMON-FAVA, STEFANIA - Tufts University
item RICHARDSON, KRIS - Tufts University
item SAXENA, RICHA - Massachusetts General Hospital
item SCHEER, FRANK - Massachusetts General Hospital
item KOVANEN, LEENA - University Of Helsinki
item BARTZ, TRACI - University Of Washington
item PERALA, MIA-MARIA - University Of Helsinki
item JONSSON, ANNA - University Of Copenhagen
item FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC)
item KALAFATI, IOANNA-PANAGIOT - Harokopio University Of Athens
item MIKKILA, VERA - University Of Turku
item PARTONEN, TIMO - University Of Helsinki
item LEMAITRE, ROZENN - University Of Helsinki
item LAHTI, JARI - University Of Helsinki
item HERNANDEZ, DENA - National Institute On Aging (NIA, NIH)
item TOFT, ULLA - University Of Copenhagen
item W CRAIG, JOHNSON - University Of Washington
item KANONI, STAVROULA - Harokopio University Of Athens
item OLLI, RAITAKARI - University Of Turku
item MARKUS, PEROLA - University Of Helsinki
item PSATY, BRUCE - University Of Washington
item FERRUCCI, LUIGI - University Of Massachusetts
item GRARUP, NIELS - University Of Copenhagen
item HEATHER, HIGHLAND - University Of Texas Health Science Center
item LOUKIANOS, RALLIDIS - University Of Athens
item KAHONEN, MIKA - University Of Turku
item HAVULINNA, AKI - Massachusetts General Hospital
item SISCOVICK, DAVID - New York City University
item RAIKKONEN, KATRI - University Of Helsinki
item TORBEN, JORGENSEN - University Of Copenhagen
item ROTTER, JEROME - University Of California
item DELOUKAS, PANOS - University Of Athens
item VIIKARI, JORMA - University Of Turku
item MOZAFFARIAN, DARIUSH - Tufts University
item LINNEBERG, ALLEN - University Of Copenhagen
item ILLKKA, SEPPALA - University Of Tampere Medical School
item HANSEN, TORBEN - University Of Copenhagen
item SALOMAA, VEIKKO - University Of Helsinki
item GHARIB, SINA - University Of Washington
item ERIKSSON, JOHAN - University Of Helsinki
item BANDINELLI, STEFANIA - University Of Florence
item PERDERSEN, OLUF - University Of Copenhagen
item RICH, STEPHEN - University Of Virginia
item DEDOUSSIS, GEORGE - Harokopio University Of Athens
item LEHTIMAKI, TERHO - University Of Turku
item ORDOVAS, JOSE - Tufts University

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/10/2014
Publication Date: 1/1/2015
Citation: Dashti, H.S., Follis, J.L., Smith, C.E., Tanaka, T., Cade, B.E., Gottlieb, D.J., Hruby, A., Jacques, P.F., Lamon-Fava, S., Richardson, K., Saxena, R., Scheer, F.A., Kovanen, L., Bartz, T.M., Perala, M., Jonsson, A., Frazier-Wood, A.C., Kalafati, I.A., Mikkila, V., Partonen, T., Lemaitre, R.N., Lahti, J., Hernandez, D.G., Toft, U., W Craig, J., Kanoni, S., Olli, R.T., Markus, P., Psaty, B.M., Ferrucci, L., Grarup, N., Heather, H.M., Loukianos, R., Kahonen, M., Havulinna, A.S., Siscovick, D.S., Raikkonen, K., Torben, J., Rotter, J.I., Deloukas, P., Viikari, J.S., Mozaffarian, D., Linneberg, A., Illkka, S., Hansen, T., Salomaa, V., Gharib, S.A., Eriksson, J.G., Bandinelli, S., Perdersen, O., Rich, S.S., Dedoussis, G., Lehtimaki, T., Ordovas, J.M. 2015. Habitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants. American Journal of Clinical Nutrition. 101(1):135-143.

Interpretive Summary: Cardiovascular disease (CVD) is one of the leading causes of preventable death in the United States. Sleep duration is a a modifiable risk factor for CVD, but little is known about the biological pathways between sleep and CVD risk. Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. We hypothesized that one pathway may act through diet, but that this pathway may be modified by variants in the CLOCK genes, as CLOCK variants are known to affect sleep timing and duration. We analyzed data across several large cohorts and observed a significant association between sleep duration and lower body mass index (BMI) in the overall sample. CLOCK variants did not modify this relationship. This has important implications for preventing CVD; these analyses recommend that in those who have short habitual sleep duration, diet is a critical factor which may prevent the onset of CVD.

Technical Abstract: 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. We examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations. We observed a significant association between sleep duration and lower BMI (Beta +/- 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. 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.