Center for Human Genetic Research Massachusetts General Hospital, 185 Cambridge Street, CPZN 5.806, Boston, MA, 02114, USA.
Diabetologia. 2014 Feb;57(2):339-46. doi: 10.1007/s00125-013-3110-y. Epub 2013 Nov 27.
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.
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.
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/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.
目的/假设：短时间和长时间睡眠与 2 型糖尿病风险增加有关。我们旨在研究空腹血糖或 2 型糖尿病的遗传变异是否与短时间或长时间睡眠有关，以及睡眠时间是否会改变遗传变异与这些特征的关联。
我们在参与候选基因关联资源（CARe）的五项研究中的欧洲血统个体中，检查了自我报告的习惯性睡眠持续时间与 2 型糖尿病患病率之间的横断面关系，共包括 1474 例病例和 8323 例对照。我们使用回归模型，在调整了年龄、性别和 BMI 后，检测了 16 个与空腹血糖相关的变异、27 个与 2 型糖尿病相关的变异以及与睡眠时间的综合遗传风险评分与连续和二分（≤5 小时或≥9 小时）睡眠时间之间的关联。最后，我们检测了基因与睡眠时间之间的相互作用是否会影响空腹血糖或 2 型糖尿病的风险。
短时间睡眠与 CARe 中的 2 型糖尿病显著相关（OR 1.32；95%CI 1.08，1.61；p=0.008）。先前与空腹血糖或 2 型糖尿病和遗传风险评分相关的变异与睡眠时间无关。此外，在血糖特征方面，没有观察到睡眠时间与这些变异之间存在研究范围内显著的相互作用。在影响 2 型糖尿病风险方面，观察到睡眠时间与 PPARG rs1801282、CRY2 rs7943320 和 HNF1B rs4430796 之间存在名义相互作用（p<0.05）。
结论/解释：我们的研究结果表明，习惯性睡眠持续时间的差异不能调节或改变与血糖特征（包括昼夜节律基因）相关的常见变异与糖尿病之间的关系。
