Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10^-8), including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10^-12) and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10^-10). The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10^-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10^-8). For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10^-16) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10^-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10^-9). Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05); undersleeping and BMI (rG = 0.147, P = 1x10^-5) and oversleeping and BMI (rG = 0.097, P = 0.04), Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and circadian rhythms in humans. Numerous studies have identified links between too little or too much sleep and circadian misalignment with metabolic disorders such as obesity and type 2 diabetes. However, cause-and-effect is not easily determined, because of multiple confounding factors affecting both sleep patterns and disease risk. Using the first release of the UK Biobank study, which combines detailed measurements and questionnaire data with genetic data, we investigate the genetics of two self-report sleep measures, chronotype and average sleep duration, in 128,266 white British individuals. We replicate previous genetic associations and identify seven and two novel genetic variants influencing chronotype and sleep duration, respectively. Associated variants are located near genes implicated in circadian rhythm regulation (RGS16, PER2), near a serotonin receptor gene (HTR6) and another gene (INADL) encoding a protein thought to be important in photosensitive retinal cells, cells known to communicate with the brain’s primary circadian pacemaker. Using the genetic risk factors, we estimate the unconfounded causal associations of BMI and type 2 diabetes on sleep patterns (and vice versa) through Mendelian Randomisation. However, we find no evidence for causal associations in either direction. The full UK Biobank release of 500,000 individuals will boost our power to detect causal associations.

Chronotype is a trait determining individual circadian preference in behavioral and biological rhythm relative to external light-dark cycle. However, little is known about the relationship between chronotype and metabolic disorders. The aim of this study was to examine whether late chronotype is related to metabolic abnormalities and body composition in middle-aged adults, independent of sleep duration and lifestyle. A total of 1620 participants aged 47-59 years were recruited from the Korean Genome and Epidemiology Study. Chronotype was assessed by the Morningness-Eveningness Questionnaire. Associations of chronotype with diabetes, metabolic syndrome, sarcopenia, and visceral obesity were analyzed. All participants underwent the oral glucose tolerance test, and body composition was measured with dual energy x-ray absorptiometry. Visceral obesity was designated as visceral fat area, measured by abdominal computed tomography, of >100 cm(2). Chronotype was classified as morning in 29.6% of subjects, evening in 5.9%, neither morning nor evening in 64.5%. Evening type, when compared with morning type, was significantly associated with diabetes (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.01-2.95), metabolic syndrome (OR, 1.74; 95% CI, 1.05-2.87), and sarcopenia (OR, 3.16; 95% CI, 1.36-7.33) after adjusting for confounding factors. Gender differences in the associations were evident. In men, evening type was associated with diabetes (OR, 2.98; 95% CI, 1.39-6.39) and sarcopenia (OR, 3.89; 95% CI, 1.33-11.33). Only metabolic syndrome was associated with evening type in women (OR, 2.22; 95% CI, 1.11-4.43). At the population level, evening chronotype was independently associated with diabetes, metabolic syndrome, and sarcopenia. These results support the importance of circadian rhythms in metabolic regulation.

S and full research articles published in SLEEP, the official journal of the APSS. Sleep and sleep disorder scientific findings.

Cho YW, et al. J Clin Neurol. 2009 Mar;5(1):20-23. http://dx.doi.org/10.3988/jcn.2009.5.1.20

Sleep, a vital process of human being, is carefully orchestrated by the brain and consists of cyclic transitions between rapid eye movement (REM) and non-REM (NREM) sleep. Autonomic tranquility during NREM sleep is characterized by vagal dominance and stable breathing, providing an opportunity for the cardiovascular-neural axis to restore homeostasis, in response to use, distress or fatigue inflicted during wakefulness. Abrupt irregular swings in sympathovagal balance during REM sleep act as phasic loads on the resting cardiovascular system. Any causes of sleep curtailment or fragmentation such as sleep restriction, sleep apnea, insomnia, periodic limb movements during sleep, and shift work, not only impair cardiovascular restoration but also impose a stress on the cardiovascular system. Sleep disturbances have been reported to play a role in the development of stroke and other cardiovascular disorders. This review aims to provide updated information on the role of abnormal sleep in the development of stroke, to discuss the implications of recent research findings, and to help both stroke clinicians and researchers understand the importance of identification and management of sleep pathology for stroke prevention and care.