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Sleep duration does not mediate or modify association of common genetic variants with type 2 diabetes
Authors:Archana Tare  Jacqueline M. Lane  Brian E. Cade  Struan F. A. Grant  Ting-hsu Chen  Naresh M. Punjabi  Diane S. Lauderdale  Phyllis C. Zee  Sina A. Gharib  Daniel J. Gottlieb  Frank A. J. L. Scheer  Susan Redline  Richa Saxena
Affiliation:1. Center for Human Genetic Research Massachusetts General Hospital, 185 Cambridge Street, CPZN 5.806, Boston, MA, 02114, USA
2. Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
3. Department of Anesthesia, Critical Care and Pain Medicine, and Harvard Medical School, Boston, MA, USA
4. Division of Sleep Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
5. Center for Applied Genomics, The Children’s Hospital of Philadelphia Research Institute, Philadelphia, PA, USA
6. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
7. Pulmonary, Allergy, Sleep and Critical Care Medicine, Boston University School of Medicine, Boston, MA, USA
8. Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA
9. Department of Health Studies, University of Chicago, Chicago, IL, USA
10. Department of Neurology and Sleep Disorders Center, Northwestern University, Chicago, IL, USA
11. Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, University of Washington, Seattle, WA, USA
12. Sleep Disorders Center, Department of Medicine, VA Boston Healthcare System, Boston, MA, USA
Abstract:

Aims/hypothesis

Short and long sleep duration are associated with increased risk of type 2 diabetes. We aimed to investigate whether genetic variants for fasting glucose or type 2 diabetes associate with short or long sleep duration and whether sleep duration modifies the association of genetic variants with these traits.

Methods

We examined the cross-sectional relationship between self-reported habitual sleep duration and prevalence of type 2 diabetes in individuals of European descent participating in five studies included in the Candidate Gene Association Resource (CARe), totalling 1,474 cases and 8,323 controls. We tested for association of 16 fasting glucose-associated variants, 27 type 2 diabetes-associated variants and aggregate genetic risk scores with continuous and dichotomised (≤5 h or ≥9 h) sleep duration using regression models adjusted for age, sex and BMI. Finally, we tested whether a gene × behaviour interaction of variants with sleep duration had an impact on fasting glucose or type 2 diabetes risk.

Results

Short sleep duration was significantly associated with type 2 diabetes in CARe (OR 1.32; 95% CI 1.08, 1.61; p?=?0.008). Variants previously associated with fasting glucose or type 2 diabetes and genetic risk scores were not associated with sleep duration. Furthermore, no study-wide significant interaction was observed between sleep duration and these variants on glycaemic traits. Nominal interactions were observed for sleep duration and PPARG rs1801282, CRY2 rs7943320 and HNF1B rs4430796 in influencing risk of type 2 diabetes (p?Conclusions/interpretation Our findings suggest that differences in habitual sleep duration do not mediate or modify the relationship between common variants underlying glycaemic traits (including in circadian rhythm genes) and diabetes.
Keywords:
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