Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population)

Marta Garaulet, Yu Chi Lee, Jian Shen, Laurence D. Parnell, Donna K. Arnett, Michael Y. Tsai, Chao Qiang Lai, Jose M. Ordovas

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Despite the importance of total energy intake in circadian system regulation, no study has related human CLOCK gene polymorphisms and food-intake measures. The aim of this study was to analyze the associations of CLOCK single-nucleotide polymorphisms (SNPs) with food intake and to explore the specific role of the cytokine system. A total of 1100 individual participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study were included. Dietary intake was estimated with a validated questionnaire. Interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP1), tumor necrosis factor-α (TNF-α), IL-2 soluble receptor-α (IL-2sR-α) and adiponectin plasma concentrations were measured. Our results showed that four of five CLOCK SNPs selected were significantly associated with total energy intake (P0.05). For SNP rs3749474, the energy intake and total fat, protein and carbohydrate intakes were significantly higher in minor allele carriers than in non-carriers. Frequency of the minor allele was greater in subjects with high energy intake than in those with low intake. Subjects with the minor allele were 1.33 times more likely to have high energy intake than non-carriers (95% CI 1.09-1.72, P0.0350). All CLOCK SNPs were associated with plasma cytokine values, in particular with those that were highly correlated with energy intake: MCP1, IL-6 and adiponectin. Interestingly, minor allele carriers with high energy intake showed decreased cytokine values, which could be related with a lower anorectic effect and decreased sleep in these subjects. In conclusion, we show a novel association of genetic variation at CLOCK with total energy intake, which was particularly relevant for SNP rs3749474. Associations could be mediated through the alteration of cytokine levels that may influence energy intake and sleep pattern.

Original languageEnglish
Pages (from-to)364-369
Number of pages6
JournalEuropean Journal of Human Genetics
Issue number3
StatePublished - Mar 2010

Bibliographical note

Funding Information:
The study sample consisted of 540 men and 560 women who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. GOLDN is part of the Program for Genetic Interactions Network and is funded by the NIH through the University of Alabama at Birmingham and in collaboration with the University of Utah, Washington University, Tufts University, University of Texas, University of Michigan, University of Minnesota and Fairview University of Minnesota Medical Center. The majority of participants were re-recruited from three-generational pedigrees from two National Heart, Lung, and Blood Institute Family Heart Study field centers (Minneapolis, Minnesota, and Salt Lake City, Utah).17 Nearly all individuals were of European descent. The details of the study are available at https:// The protocol was approved by the institutional review boards of the University of Alabama, the University of Minnesota, the University of Utah and the Tufts University. To avoid using data from under-reporters of total energy intake, all subjects who reported less than 600 kcal/day of energy intake were excluded from the study, resulting in a final sample size of 1100 individuals.

Funding Information:
This work was supported by the Seneca Foundation from the Government of Murcia (project 02934/PI/05 to MG), the Government of Education, Science and Research of Murcia (Project BIO/FFA 07/01-0004) and by The Spanish Government of Science and Innovation (projects AGL2008-01655/ALI) and by Grants U01 HL72524 and HL-54776 from the National Institutes of Health, and DK075030 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service. JMO.


  • Circadian
  • Energy intake
  • Interleukin-6
  • Metabolic syndrome
  • Obesity

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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