Morselli Lisa L, Gamazon Eric R, Tasali Esra, Cox Nancy J, Van Cauter Eve, Davis Lea K
Sleep, Metabolism and Health Center, Department of Medicine, The University of Chicago, Chicago, IL
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA.
Diabetes. 2018 Jan;67(1):155-164. doi: 10.2337/db16-1229. Epub 2017 Oct 30.
Over the past 20 years, a large body of experimental and epidemiologic evidence has linked sleep duration and quality to glucose homeostasis, although the mechanistic pathways remain unclear. The aim of the current study was to determine whether genetic variation influencing both sleep and glucose regulation could underlie their functional relationship. We hypothesized that the genetic regulation of electroencephalographic (EEG) activity during non-rapid eye movement sleep, a highly heritable trait with fingerprint reproducibility, is correlated with the genetic control of metabolic traits including insulin sensitivity and β-cell function. We tested our hypotheses through univariate and bivariate heritability analyses in a three-generation pedigree with in-depth phenotyping of both sleep EEG and metabolic traits in 48 family members. Our analyses accounted for age, sex, adiposity, and the use of psychoactive medications. In univariate analyses, we found significant heritability for measures of fasting insulin sensitivity and β-cell function, for time spent in slow-wave sleep, and for EEG spectral power in the delta, theta, and sigma ranges. Bivariate heritability analyses provided the first evidence for a shared genetic control of brain activity during deep sleep and fasting insulin secretion rate.
在过去20年里，大量实验和流行病学证据已将睡眠时间和质量与葡萄糖稳态联系起来，尽管其作用机制尚不清楚。本研究的目的是确定影响睡眠和葡萄糖调节的基因变异是否可能是它们功能关系的基础。我们假设，非快速眼动睡眠期间脑电图（EEG）活动的基因调控，这是一种具有指纹再现性的高度可遗传特征，与包括胰岛素敏感性和β细胞功能在内的代谢特征的基因控制相关。我们通过对一个三代家系进行单变量和双变量遗传力分析来检验我们的假设，该家系对48名家庭成员的睡眠脑电图和代谢特征进行了深入的表型分析。我们的分析考虑了年龄、性别、肥胖和精神活性药物的使用情况。在单变量分析中，我们发现空腹胰岛素敏感性和β细胞功能指标、慢波睡眠时长以及δ、θ和σ频段的脑电图频谱功率具有显著的遗传力。双变量遗传力分析首次为深度睡眠期间的大脑活动和空腹胰岛素分泌率的共同基因控制提供了证据。
