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Sleep duration does not mediate or modify association of common genetic variants with type 2 diabetes.

TitleSleep duration does not mediate or modify association of common genetic variants with type 2 diabetes.
Publication TypeJournal Article
Year of Publication2014
AuthorsTare, A, Lane, JM, Cade, BE, Grant, SFA, Chen, T-H, Punjabi, NM, Lauderdale, DS, Zee, PC, Gharib, SA, Gottlieb, DJ, Scheer, FAJL, Redline, S, Saxena, R
JournalDiabetologia
Volume57
Issue2
Pagination339-46
Date Published2014 Feb
ISSN1432-0428
KeywordsBlood Glucose, Body Composition, Body Mass Index, Cross-Sectional Studies, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Fasting, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Glucose Intolerance, Glycated Hemoglobin A, Humans, Insulin Resistance, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Sleep, Surveys and Questionnaires, Time Factors, United States
Abstract<p><b>AIMS/HYPOTHESIS: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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).</p><p><b>CONCLUSIONS/INTERPRETATION: </b>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.</p>
DOI10.1007/s00125-013-3110-y
Alternate JournalDiabetologia
PubMed ID24280871
PubMed Central IDPMC4006271
Grant ListN01HC55222 / HC / NHLBI NIH HHS / United States
8UL1TR000170-05 / TR / NCATS NIH HHS / United States
U01HL53937 / HL / NHLBI NIH HHS / United States
N01HC85080 / HC / NHLBI NIH HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
R01 HL113338 / HL / NHLBI NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
U01HL53934 / HL / NHLBI NIH HHS / United States
N01HC85081 / HC / NHLBI NIH HHS / United States
N01HC85079 / HC / NHLBI NIH HHS / United States
UL1 TR000439 / TR / NCATS NIH HHS / United States
N01HC85086 / HC / NHLBI NIH HHS / United States
U01HL63429 / HL / NHLBI NIH HHS / United States
N01HC85082 / HC / NHLBI NIH HHS / United States
U01HL53941 / HL / NHLBI NIH HHS / United States
U01HL53916 / HL / NHLBI NIH HHS / United States
R21 DK089378 / DK / NIDDK NIH HHS / United States
R21 HL121728 / HL / NHLBI NIH HHS / United States
UL1 RR025758 / RR / NCRR NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01HC85083 / HC / NHLBI NIH HHS / United States
AG023629 / AG / NIA NIH HHS / United States
U01HL63463 / HL / NHLBI NIH HHS / United States