CRY1 circadian gene variant interacts with carbohydrate intake for insulin resistance in two independent populations: Mediterranean and North American

Hassan S. Dashti, Caren E. Smith, Yu Chi Lee, Laurence D. Parnell, Chao Qiang Lai, Donna K. Arnett, José M. Ordovás, Marta Garaulet

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Dysregulation in the circadian system induced by variants of clock genes has been associated with type 2 diabetes. Evidence for the role of cryptochromes, core components of the system, in regulating glucose homeostasis is not supported by CRY1 candidate gene association studies for diabetes and insulin resistance in human, suggesting possible dietary influences. The purpose of this study was to test for interactions between a CRY1 polymorphism, rs2287161, and carbohydrate intake on insulin resistance in two independent populations: a Mediterranean (n = 728) and an European origin North American population (n = 820). Linear regression interaction models were performed in two populations to test for gene-diet interactions on fasting insulin and glucose and two insulin-related traits, homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI). In addition, fixed effects meta-analyses for these interactions were performed. Cohort-specific interaction analyses showed significant interactions between the CRY1 variant and dietary carbohydrates for insulin resistance in both populations (p < 0.05). Findings from the meta-analyses of carbohydrate-single nucleotide polymorphism interactions indicated that an increase in carbohydrate intake (% of energy intake) was associated with a significant increase in HOMA-IR (p = 0.011), fasting insulin (p = 0.007) and a decrease in QUICKI (p = 0.028), only among individuals homozygous for the minor C allele. This novel finding supports the link between the circadian system and glucose metabolism and suggests the importance this CRY1 locus in developing personalized nutrition programs aimed at reducing insulin resistance and diabetes risk.

Original languageEnglish
Pages (from-to)660-667
Number of pages8
JournalChronobiology International
Issue number5
StatePublished - Jun 2014

Bibliographical note

Funding Information:
The study sample consisted of 820 (50.5%) women (age: mean = 48.3 years, SD = 15.9 years; BMI: mean = 28.5 kg/m2, SD = 5.5 kg/m2) 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, MN and Salt Lake City, UT) (Higgins et al., 1996). Nearly all individuals were of European descent. The details of the study are available at https:// The protocol was previously approved by the institutional review boards at each of the above-referenced institutions.

Funding Information:
The authors declare no conflict of interest. This study was supported by grants from Tomás Pascual and Pilar Gómez-Cuétara Foundations, Spanish Government of Science and Innovation (BFU2011-24720), Séneca Foundation from the Government of Murcia (15123/ PI/10). National Heart, Lung, and Blood Institute grants HL-54776, National Institute of Diabetes and Digestive and Kidney Diseases, Grant Number DK075030 and by contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research. C. Smith is supported by K08 HL112845.


  • CRY1
  • Carbohydrate intake
  • Diabetes
  • Gene-diet interaction
  • Genetic epidemiology

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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