title: Sleep duration does not mediate or modify association of common genetic variants with type 2 diabetes.
abstract: OBJECTIVE
  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 < 0.05).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Human Genetic Research Massachusetts General Hospital, 185 Cambridge Street, CPZN 5.806, Boston, MA, 02114, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Tare
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Lane
authors.forename: Brian E
authors.initials: BE
authors.lastname: Cade
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Ting-Hsu
authors.initials: TH
authors.lastname: Chen
authors.forename: Naresh M
authors.initials: NM
authors.lastname: Punjabi
authors.forename: Diane S
authors.initials: DS
authors.lastname: Lauderdale
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Zee
authors.forename: Sina A
authors.initials: SA
authors.lastname: Gharib
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Gottlieb
authors.forename: Frank A J L
authors.initials: FA
authors.lastname: Scheer
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D005215:Fasting; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D018149:Glucose Intolerance / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012890:Sleep / Q000502:physiology*; D011795:Surveys and Questionnaires; D013997:Time Factors; D014481:United States; D044465:White People / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human